Abstract: The present invention is directed to a method for the treatment of hemophilia.

Abstract: Provided herein are methods and compositions for producing Factor VIII proteins. Such methods include introducing into a cell a nucleic acid molecule encoding a Factor VIII protein operably linked to a promoter, wherein the promoter is characterized by the ability to produce commercially viable Factor VIII protein; and incubating the cell under conditions for producing commercially viable Factor VIII protein. Also provided are nucleic acid molecules which encode a Factor VIII protein operably linked to a Chinese hamster elongation factor 1-? (CHEF1) promoter, which may be used in the methods provided herein.

Abstract: The present invention provides methods for predicting the risk of an individual developing antibodies to factor VIII by identifying a single nucleotide polymorphism of an immune response or immune modifier gene. The invention further provides oligonucleotides, diagnostic kits, microarrays, and isolated nucleic acids comprising single nucleotide polymorphisms of immune response or immune modifier genes.

Abstract: A Factor VIII derivative of formula (I): wherein: B represents C2 to C10 alkylene; m represents 0 or an integer from 1 to 19, n represents an integer from 1 to 20, and the sum of m and n is from 1 to 20; P represents a mono or polyradical of Factor VIII obtained by removing m+n carbamoyl groups from the side chains of glutamine residues in Factor VIII; and M represents a moiety (M1) that increases the plasma half-life of the Factor VIII derivative or a reporter moiety (M2); or a pharmaceutically acceptable salt thereof.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: The present inventors succeeded in constructing bispecific antibodies, which bind to both the blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X, and functionally substitute for blood coagulation factor VIII/activated blood coagulation factor VIII which enhances the enzymatic reaction.

Abstract: Provided herein are methods and compositions for purifying human factor VIII, human factor VIII-like peptide or fragments thereof. The methods comprise immobilizing a binding molecule for human factor VIII, human factor VIII-like protein or fragments thereof to a solid support, contacting the immobilized binding molecule with a solution containing the human factor VIII, human factor VIII-like protein or fragments thereof, and purifying the factor by separating the solution from the solid support.

Abstract: A method of treating a patient suffering from Haemophilia A and/or Von Willebrand's disease involves administering the patient a concentrate of Von Willebrand Factor (VWF) or a complex of Factor VIII/VWF prepared by creating a solution of VWF or a complex of Factor VIII/VWF containing VWF at a concentration of up to 12 IU VWF:RCo/ml and a VWF/Factor VIII ratio of 0.4 or more, and nanofiltering that starting solution through a filter of pore size of about 35 nm or smaller. The resulting VWF retains high molecular weight multimers.

Abstract: Methods for treating bleeding disorders using non-anticoagulant sulfated polysaccharides (NASPs) as procoagulants are disclosed. NASPs can be administered as single agents, or in combination with one another, or with other medications (such as factors VII, VIII and IX) to promote hemostasis. In particular, the use of NASPs in treatment of bleeding disorders, including congenital coagulation disorders, acquired coagulation disorders, and trauma induced hemorrhagic conditions is described.

Abstract: A method of modulating transplant organ size in a subject in need thereof is disclosed. The method comprising: (a) administering to the subject an agent capable of modulating an activity or expression of a coagulation factor or an effector thereof; and (b) transplanting the organ into the subject; thereby modulating the transplant organ size in the subject.

Abstract: A polymeric prodrug composition including a hydrogel, a biologically active moiety and a reversible prodrug linker. The prodrug linker covalently links the hydrogel and the biologically active moiety at a position and the hydrogel has a plurality of pores with openings on its surface. The diameter of the pores is larger than that of the biologically active moiety at least at all points of the pore between at least one of the openings and the position of the biologically active moiety.

Abstract: The invention relates to conjugated proteins, in particular but not exclusively, blood coagulation factors, to processes for preparing said conjugates, to pharmaceutical compositions comprising said conjugates and to the use of the conjugates in therapy, in particular but not exclusively, for the treatment of diseases alleviated by blood coagulation factors such as the prophylactic treatment of hemophilia.

Abstract: Conjugates of hydroxyalkyl starch and a protein are provided herein. The conjugates are formed by a convalent linkage between the hydroxyalkyl starch or a derivative of the hydroxyalkyl starch and the protein. Methods of producing the conjugates and the use of the conjugates also are provided herein.

Abstract: The present invention relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.

Abstract: A histidine-free composition comprising: a high purity factor VIII (r-factor VIII); arginine and/or sucrose; a surface-active agent to prevent or at least inhibit surface adsorption of factor VIII; an amount of calcium chloride for specific stabilization of factor VIII.

Abstract: Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.

Abstract: An aqueous composition which comprises a protein or other biological molecule and also (i) optionally comprises one or more metal ions at a concentration of 0.01 to 20 mM; (ii) comprises excipients which are weak ligands; and (iii) is substantially free of excipients which are medium-strength ligands or strong ligands.

Abstract: The invention concerns glycosylated proteins having human factor VIII activity. In a preferred embodiment, the protein is glycosylated with oligosaccharides that include an alpha-(2,6)-linked sialic acid and a bisecting GlcNAc linked to a core beta-mannose.

Abstract: Provided are lipidic particles comprising phosphatidylcholine, phosphatidylinositol and cholesterol. Also provided are compositions comprising the lipidic particles and having associated therewith therapeutic agents such as peptides, polypeptides or proteins. In these compositions, the therapeutic agents have reduced immunogenicity and/or longer circulating time. These compositions can be used for therapeutic administration of the peptides, polypeptides and/or proteins.

Abstract: The present invention relates to modified nucleic acid sequences coding for coagulation factors, in particular human Factor VIII and their derivatives with improved stability, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives which do have biological activities of the unmodified wild type protein but having improved stability and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises modified DNA sequences.

Abstract: The present invention relates generally to methods and compositions for treating a disease or condition by administering a first therapeutic protocol comprising targeting and delivering solid-phase platelet-dependent vascular occlusion agents, and administering at least one second therapeutic composition or method.

Abstract: Factor VIII polypeptides having FVIII:C activity that contain modifications in the A3 and/or C1 and/or C2 domains of the sequence of the light chain of Factor VIII, characterized by the binding affinity to low density lipoprotein receptor protein, and methods for producing the same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention relates to modified Factor VIII molecules with reduced N-linked glycosylation and reduced immunogenicity. The invention also relates to methods of using modified Factor VIII molecules, for example, to treat patients afflicted with hemophilia.

Abstract: A method of factor XI-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject. A method of factor XI-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising: (i) selecting a subject that is not deficient for factor XI; and (ii) administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject, wherein the NASP enhances blood coagulation in a factor XI-dependent manner.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The invention is a proteinaceous construct comprising a Factor VIII molecule which is conjugated to a water-soluble polymer via carbohydrate moieties of Factor VIII, and methods of preparing same.

Abstract: The present invention relates to a von Willebrand Factor for use in the treatment and/or prevention of a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes. Furthermore, the present invention relates to a method of treating and/or preventing a disorder related to a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes comprising administering a pharmaceutically effective amount of a von-Willebrand-Factor (vWF) to a patient in need thereof. The present invention also relates to a composition comprising vWF and a composition comprising FVIII for simultaneous, separate or sequential use for use in the treatment and/or prevention of a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes.

Abstract: A method of preparing an oxidised polysaccharide-protein conjugate by oxidising a polysaccharide with an oxidising agent to form an oxidised polysaccharide and combining such oxidized polysaccharide with a protein. The oxidised polysaccharide is reacted with a protein to form a composition comprising a conjugate wherein the oxidised polysaccharide and the protein are conjugated via one or more imine bonds and wherein the oxidised polysaccharide comprises essentially no alpha-hydroxy aldehyde units. The conjugate may be used to provide sustained or latent activity of the protein.

Abstract: Methods and compositions are provided that allow for high-level expression of a factor VIII polypeptide. More specifically, methods and compositions are provided comprising nucleic acid and amino acid sequences comprising a modified factor VIII that result in high-level expression of the polypeptide. The methods and compositions of the invention find use in the treatment of factor VIII deficiency including, for example, hemophilia A.

Abstract: The present invention relates, generally, to a transgenic non-human animal model of hemophilia A, wherein the transgenic animal is deficient in endogenous Factor VIII and endogenous von Willebrand Factor, and methods to treat hereditary or acquired hemophilia A or von Willebrand Disease (VWD) by administration of exogenous human VWF.

Abstract: The invention provides a method for preventing formation of inhibitors to blood coagulation factor VIII or factor IX in a subject having haemophilia, the method comprising administering (via intravenous, subcutaneous, intradermal, or intramuscular routes) to a previously untreated subject an effective dosage of factor VIIa or a factor VII-related polypeptide.

Abstract: The present invention relates to a proteinaceous construct (also designated as polymer-VWF-conjugate) comprising plasmatic and/or recombinant von Willebrand factor (VWF), said VWF being bound to at least one physiologically acceptable polymer molecule, as well as to a complex between said proteinaceous construct and at least one factor VIII (FVIII) protein. The physiologically acceptable polymer molecule can be, for instance, polyethylene glycol (PEG) or polysialic acid (PSA). Further the present invention relates to methods for prolonging the in vivo-half-life of VWF or FVIII in the blood of a mammal having a bleeding disorder associated with functional defects of or deficiencies of at least one of FVIII or VWF.

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: This invention relates in general to a method and device for facilitating hemostasis and wound healing. In particular, the invention relates to the device comprising a polymeric material disposed on a scaffold that facilitates hemostasis and wound healing. Specifically, the invention contemplates the use of such scaffolds in conjunction with a negative pressure device.

Abstract: The invention relates to storable medicaments produced from pharmaceutical active ingredient preparations which are virus safe. Said medicaments contain at least one intact therapeutic protein obtained from plasma or by means of genetic engineering, as an active pharmaceutical substance. Said active ingredient preparations contain active enzymes, especially proteases, which are either free or bound to the substrates thereof and act against the therapeutic protein(s) present.

Abstract: The invention relates to novel compounds with formula (I) X1-X2-X3-X4-X5-(X6)n-(X7)m-Y useful as blood coagulation factor inhibitors. The compounds (I) may be used for treatment of thrombotic conditions or as stabilizers of liquid formulations of blood coagulation factors, in particular liquid formulations of FVIIa, Factor VII variants, or Factor VII derivatives.

Abstract: The present invention relates to new antibodies and fragments and derivatives thereof. These antibodies bind to the A2 domain of Factor VIII (FVIII) of the coagulation pathway and inhibit the coagulation activity of FVIII. The antibodies are particularly suited for the characterization of the structure and function of FVIII, for the design of therapeutic strategies for eradication of FVIII inhibitors and for the use as a medicament. The invention also relates to cell lines producing the specific antibodies. The present invention furthermore relates to pharmaceutical compositions comprising the antibodies, fragments and/or derivatives of the invention and to methods of preventing and treating cardiovascular disorders by using the antibodies or fragments and derivatives thereof or pharmaceutical compositions thereof.

Abstract: This invention provides methods for modifying glycosylation patterns of glycopeptides, including recombinantly produced glycopeptides. Also provided are glycopeptide compositions in which the glycopeptides have a uniform glycosylation pattern.

Abstract: The present invention provides a peptide comprising a core residue sequence derivable from human FVIII which peptide is capable of binding to an MHC class II molecule without further antigen processing. The present invention also relates to the use of such peptides for the prevention or suppression of inhibitor antibody formation in haemophilia A and/or acquired haemophilia.

Abstract: The present invention relates to improved human FVIII variants having at least one substitution in the A2 and/or C2 domain. The present invention also relates to their uses in the treatment of hemophilia A, particularly in patients with inhibitors.

Abstract: The present invention relates to the use of von Willebrand Factor (VWF) preparations or of a VWF preparation in combination with coagulation Factor VIII (FVIII) for extravascular administration in the therapy and prophylactic treatment of bleeding disorders.

Abstract: Disclosed are compositions and methods related to Factor VIII.

Abstract: This invention relates to methods for the stabilization, storage and delivery of biologically active macromolecules, such as proteins, peptides and nucleic acids. In particular, this invention relates to protein or nucleic acid crystals, formulations and compositions comprising them. Methods are provided for the crystallization of proteins and nucleic acids and for the preparation of stabilized protein or nucleic acid crystals for use in dry or slurry formulations. The present invention is further directed to encapsulating proteins, glycoproteins, enzymes, antibodies, hormones and peptide crystals or crystal formulations into compositions for biological delivery to humans and animals. According to this invention, protein crystals or crystal formulations are encapsulated within a matrix comprising a polymeric carrier to form a composition.