Abstract: Provided herein are modified FVII polypetides, and modified FVIIa polypeptides, and methods of treatment of acute and episodic bleeding with modified FactorVIIa polypeptides. To effect treatment and use, in some embodiments, the modified polypeptides are subcutaneously administered to provide on-demand treatment. In some embodiments, the on-demand treatment is provided in a multiple dosing regimen over a twenty-four hour period. The subcutaneous administration of the modified polypeptides of the disclosure exhibit increased coagulant activity, potency, bioavailablilty and prolonged duration.

Abstract: The present invention relates to a method for the purification of divalent cation binding proteins with high purity on an anion exchange resin material, to divalent cation binding proteins obtainable by said method, and to a kit comprising means for carrying out said method.

Abstract: The present invention provides a therapeutic agent for epithelial and endothelial injury, and in particular, for epithelial and endothelial microinjury, and the like. The therapeutic agent according to the present invention comprises, for example, a peptide of the following (a), (b), etc., a derivative thereof, or their salt: (a) a peptide comprising the amino acid sequence shown in any one of SEQ ID NOS: 10, 4, 12 and 6; or (b) a peptide comprising the amino acid sequence shown in any one of SEQ ID NOS: 16, 18, 20 and 22.

Abstract: The present invention relates to a two-step method for the purification of divalent cation binding proteins with high yield and high purity on anion exchange resin materials, to divalent cation binding proteins obtainable by said method, and to a kit comprising means for carrying out said method.

Abstract: Conjugates of a Factor IX moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is polyethylene glycol) or a derivative thereof. Also provided (among other things) are compositions comprising the conjugates, methods of making the conjugates, and methods of administering to a patient compositions comprising the conjugates.

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract: The present invention relates to modified coagulation Factor VII polypeptides exhibiting increased resistance to antithrombin inactivation and enhanced proteolytic activity. The present invention also relates to polynucleotide constructs encoding such polypeptides, vectors and host cells comprising and expressing such polynucleotides, pharmaceutical compositions, uses and methods of treatment.

Abstract: The invention provides a genipin cross-linked fibrin gel. The ratio of genipin to fibrin in the gel ranges from about 0.1:1 to about 10:1 (genipin:fibrin). The gel can be hydrogel. Also provided is method for repairing tissue defects by administering the gel to site of tissue defect.

Abstract: The invention relates to materials and methods of conjugating a water soluble fatty acid derivative to a therapeutic protein comprising contacting the therapeutic protein with an activated water soluble fatty acid derivative under conditions that allow conjugation.

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract: The synergistic biomolecule-polymer conjugates are the long-acting, in vivo controlled continuous-release and hybrid synergy systems of biomolecules that provide increased biological activities and enhanced pharmacological properties for achieving greater therapeutic efficacies.

Abstract: This invention is directed to the use of a chorionic gonadotrophin carboxy terminal peptide (CTP) or fragments thereof for modifying a polypeptide or a fragment thereof in order to increase the hydrodynamic volume of the polypeptide or fragment thereof.

Abstract: The invention relates to conjugated proteins, in particular but not exclusively, blood coagulation factors, to processes for preparing the conjugated proteins which contain the steps of reacting a protein or glycoprotein, such as factor VIIa or human growth hormone, with a water insoluble albumin binder in the presence of an optionally substituted cyclodextrin molecule, to pharmaceutical compositions comprising the protein conjugates and to the use of the protein 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: The present application relates to methods for purifying recombinant coagulation factor proteins, including for example, prothrombin (Factor II). In embodiments, the methods provide purified prothrombin that exhibit increased bioactivity and reduced levels of thrombin, thereby increasing the safety of the prothrombin. Also provided are purified recombinant coagulation factor proteins.

Abstract: The present invention relates to compositions comprising biologically active proteins linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of glucose-related diseases, metabolic diseases, coagulation disorders, and growth hormone-related disorders and conditions.

Abstract: The present invention relates, in general, to methods for detecting and quantitating plasma-derived protein and recombinant protein in a sample based on the difference in protein glycosylation, when the plasma protein and the recombinant protein are essentially the same protein.

Abstract: The invention relates to a chimeric protein comprising at least one clotting factor and at least a portion of an immunoglobulin constant region. The invention relates to a method of treating a hemostatic disorder comprising administering a therapeutically effective amount of a chimeric protein wherein the chimeric protein comprises at least one clotting factor and at least a portion of an immunoglobulin constant region.

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: The present invention relates to the fields of Factor VII (FVII) and Factor VIIa (FVIIa) albumin linked polypeptides. More specifically, the invention relates to cDNA sequences coding for human Factor VII and Factor VIIa and derivatives genetically fused to a cDNA coding for human serum albumin which may be linked by oligonucleotides which code for intervening peptidic linkers such encoded derivatives exhibiting improved stability and extended functional plasma half-life, recombinant expression vectors containing such cDNA 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 prolonged shelf-life 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 such modified DNA sequences.

Abstract: Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.

Abstract: The present disclosure provides, inter alia, formulation compositions comprising modified nucleic acid molecules which may encode a protein, a protein precursor, or a partially or fully processed form of the protein or a protein precursor. The formulation composition may further include a modified nucleic acid molecule and a delivery agent. The present invention further provides nucleic acids useful for encoding polypeptides capable of modulating a cell's function and/or activity.

Abstract: ClotBlock is a lyophilized fibrin hemostatic designed for use an adjunct or primary treatment in moderate to severe hemorrhage. It can be applied directly to the wound in a laparotomy procedure or as non-invasive sealant. Its crosslinking technology generates a strong and safe adhesive fibrin sealant required for high volume hemostasis. The attachment properties of the cake as well as the rapid formation of and stability of the fibrin clot ensures that a strong stable fibrin clot is formed within 1 to 5 minutes depending on the grade of the wound. The agent is safe, biocompatible, biodegradable and can be stored at room temperature for one year.

Abstract: Intra-arterial administering at least one blood coagulation to a bleeding patient is provided, together with a pharmaceutical composition therefor.

Abstract: The present invention relates to compositions comprising factor VII coagulation factors linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in treatment of coagulation factor-related diseases, disorders, and conditions.

Abstract: The present invention relates to factor IXa complexes and crystals thereof as well as methods for identifying inhibitors of factor IXa.

Abstract: The invention relates to a method of purifying PEGylated proteins by removing impurities from samples containing PEGylated proteins, in particular, but not exclusively vitamin K-dependent blood coagulation factors such as Factor IX (FIX), to proteins purified by said method and to the use of said purified proteins 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: The invention is directed to blood proteins produced in monocot seeds and isolated therefrom for use in therapeutic compositions, as well as to methods of making these isolated blood proteins and to therapeutic compositions comprising them.

Abstract: A Factor X (hereinafter referred to as “FX”) with a high activity is provided. The present invention relates to a method for efficiently preparing a recombinant, two-chain FX which comprises intervening glycosylation at such an amino acid sequence that is essential for glycosylation in FX to thereby allow for expression of a recombinant FX with no glycosylation, and the recombinant FX with no glycosylation obtained by said method.

Abstract: The invention relates to chemically as well as physically stable kits and compositions comprising polypeptides, in particular Factor VII or Factor VII-related polypeptides, such that these compositions can be stored, handled and used at room temperature.

Abstract: Methods and cell lines for overexpressing functional gamma-carboxylated proteins are disclosed by way of genetically engineered cell lines which over-express VKORC1. Also disclosed is the antisense inhibition of expression of calumenin in conjunction with overexpression of VKORC1 which also increases expression of functional gamma-carboxylated proteins. Gamma-carboxylated proteins of interest may include blood coagulation factors such as human clotting factors IX and VII.

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: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a blood coagulation protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer. In one embodiment of the invention the conjugation is carried out in the presence of the nucleophilic catalyst aniline. In addition the generated oxime linkage can be stabilized by reduction with NaCNBH3 to form an alkoxyamine linkage.

Abstract: The present invention relates to method for selective reduction and derivatization of recombinantly prepared engineered proteins comprising at least one non-native cysteine, wherein the reduction reaction is conducted in the presence of a redox buffer or in the presence of a triarylphosphine reducing agent.

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: The invention is related to a process for separating proteins fibrinogen, Factor XIII and biological glue from a solubilized plasma fraction and for preparing freeze-dried concentrates of said proteins comprising the steps of: chromatographic purification comprising the steps of loading an anion exchanger of weak base type with the said solubilized fraction, previously equilibrated with a buffer of a predetermined ionic strength of an alkaline pH, which allows to retain the biological glue, elution of the biological glue by increasing the ionic strength of the said buffer, and separation of FXIII from fibrinogen by addition to at least one part of the biological glue eluate of at least one chemical agent precipitating the FXIII, and recovery of the resulting purified fibrinogen containing supernatant solution, and diafiltration of the fibrinogen, biological glue and resolubilized FXIII solutions, followed by a freeze-drying of said solutions.

Abstract: Conjugates of a Factor IX moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided (among other things) are compositions comprising the conjugates, methods of making the conjugates, and methods of administering to a patient compositions comprising the conjugates.

Abstract: Disclosed is a fusion protein comprising blood coagulation factor IX (FIX) and transferrin. The fusion protein exhibits improved specific FIX activity, as compared to native FIX, and can be useful in the treatment of FIX deficiency-associated diseases.

Abstract: The present invention relates to chimeric derivatives of serine protease zymogen containing the activation peptide of factor X or a fragment thereof for improving the half-life of said derivatives. Preferably, said chimeric derivatives are protein C and factor X derivatives. The invention also relates to said derivatives for the prevention or treatment of blood coagulation disorders.

Abstract: Provided are storage containers for proteinaceous pharmaceutical compositions which are characterized in, among other things, comprising (i) a wall portion, wherein an inner wall material thereof is selected from silica-coated glass, silicone-coated glass, polymers of non-cyclic olefins, cycloolefin polymers and cycloolefin/linear olefin copolymers and (ii) one or more closure portions not constituting part of the wall portion, and which contains a formulation of a protein. Also provided are new methods of storing proteinaceous compositions. In one aspect, the stored protein is characterized as having an amino-terminal ?-carboxyglutamic acid (Gla) domain with 9-12 Gla residues.

Abstract: Modified factor VII polypeptides and uses thereof are provided. Such modified FVII polypeptides include Factor VIIa and other forms of Factor VII. Among modified FVII polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics.

Abstract: The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having factor VIII (FVIII) independent factor X (FX) activation potential. Five full length FIX proteins with combinations of mutations of amino acids important for functional activity of FIX and FIX wild type were cloned and expressed in HEK 293 cells. The proteins were tested by an activated partial thromboplastin time (aPTT) assay in FVIII-depleted plasma as well as in FVIII-inhibited patient plasma. In FVIII-depleted plasma functional activity of the FIX mutants was calculated as increased FVIII equivalent activity. The mutant proteins had increased FVIII equivalent activity. In FVIII-inhibited patient plasma the FEIBA equivalent activity was calculated for analysis of FVIII independent FX activation potential. The proteins had also increased FEIBA equivalent activity. Furthermore, the pre-activated FIX proteins had an increased activity in FIX-depleted plasma containing FVIII inhibitors.

Abstract: The synergistic biomolecule-polymer conjugates are the long-acting, in vivo controlled continuous-release and hybrid synergy systems of biomolecules that provide increased biological activities and enhanced pharmacological properties for achieving greater therapeutic efficacies.

Abstract: The invention relates generally to compositions and methods for purifying the desired species from a mixture of desired heterodimer and contaminating homodimer immunoglobulin variants by modifying the isoelectric point(s) of the individual chains.

Abstract: Polypeptides and polynucleotides encoding same comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotrophin attached to a carboxy terminus of a coagulation factor and not to an amino terminus are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using same are also disclosed.

Abstract: The present invention relates to a method for the purification of rFIX using anion exchange chromatography in the pseudo-affinity mode, wherein said method comprises a wash step with a wash buffer having a salt concentration of more than 200 mM. The purification according to the invention provides a method to enrich rFIX molecules which have been posttranslationally modified by sulfation and/or phosphorylation. The present invention further relates to purified rFIX compositions enriched in monosulfated and/or monophosphorylated rFIX molecules.

Abstract: The present invention provides methods for the local treatment of bleeding in a subject and/or reducing unwanted effects associated with the systemic administration of thrombotic agents to a subject, by local administration of FVII to the subject.

Abstract: A method is disclosed for filtering a protein in a liquid mixture in a manner that does not substantially damage or otherwise limit the recovery of the protein in the filtration filtrate. The method generally includes passing a liquid mixture containing a protein (e.g., an aqueous vWF mixture) through a filter while applying a counter pressure to the liquid mixture filtrate to accurately reduce and control the pressure differential across the filter. The disclosed method has the advantage that relatively high filtration flow rates can be achieved at relatively low pressure differentials, in contrast to high pressure differentials, which actually reduce the filtration flow rate of protein liquid mixtures. Further, the method can recover substantially all of the protein that is initially present in the liquid mixture.

Abstract: The present invention relates to antidotes of anticoagulants targeting factor Xa which antidotes are used in combination with blood coagulating agents or other heparin antidotes to prevent or reduce bleeding in a subject. The antidotes described herein have reduced or no intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is or will be undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract: A method for stabilising a human blood protein or human blood plasma protein with a molecular weight of >10 KDa by adding melezitose to a solution comprising the human blood protein or human blood plasma protein with a molecular weight of >10 KDa.

Abstract: The present invention provides methods for the local treatment of tracheal, bronchial or alveolar bleeding or hemoptysis and/or reducing unwanted effects associated with systemic administration of thrombotic agents to a subject via intratracheal, intrabronchial or intraalveolar administration of a blood coagulation factor to the subject.