Abstract: The present invention is directed to a method of inactivating virus that is present during production of a polypeptide of interest. In particular, the present invention is directed to a method of on-column virus inactivation using a low pH and high salt wash solution that effectively inactivates viruses with minimum recovery loss of the polypeptide.

Abstract: The present invention relates to the field of chromatography. More closely, the invention relates to a chromatographic method for purification of plasmaproteins, such as Factor VIII, von Willebrand factor and Factor IX. The chromatographic method is performed on a matrix comprising an inner porous core and outer porous lid surrounding said core.

Abstract: A method of hemostasis includes the step of applying a hemostatic agent to an affected site of a subject, the hemostatic agent consisting of a first agent comprising a gelatin derivative having a hydrophobic group bonded to the gelatin via an imino group, wherein the gelatin derivative has (a) a weight average molecular weight of from 10,000 to 50,000, (b) the hydrophobic group, which is an alkyl group having 6 to 18 carbon atoms; and (c) a molar ratio of imino group/amino group of the gelatin derivative ranging from 1/99 to 30/70; and a second agent including a crosslinking agent for the gelatin derivative.

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 application provides methods of prevention and/or treatment of breast cancer in a subject by inhibiting expression of PAX2. In the cancer treatment methods disclosed, the method of inhibiting expression of PAX2 can be by administration of a nucleic acid encoding an siRNA for PAX2. A method of treating cancer in a subject by administering DEFB1 is also provided. Similarly, provided is a method of treating cancer in a subject by increasing expression of DEFB1 in the subject.

Abstract: The present invention relates to a factor VII composition having a substantially homogeneous isoelectric point and to a method for formulating such a composition. The present invention also relates to the therapeutic use of a factor VII composition having a substantially homogeneous isoelectric point.

Abstract: The present invention provides a method of purifying multimeric von Willebrand Factor (VWF) from a solution comprising multimeric VWF and contaminants. The method comprises passing the solution through a chromatography column comprising beads of a mixed mode chromatography resin coated with a size-exclusion inactive shell and collecting the multimeric VWF which passes through the column without binding to the resin.

Abstract: Compositions and methods are described for preventing or reducing protein loss due to protein aggregation, denaturation, and adsorption to surfaces. Also described are compositions and methods for preventing or reducing the fouling or clogging of medical devices that come into contact with blood, such as catheters. Also described are methods to treat diseases caused by activation of the microvasculature.

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 a method or process for the manufacture of a virus and prion save native fibrinogen concentrate of high purity and low amounts of fibrinopeptide A and fibronectin.

Abstract: The present invention provides methods of administering Factor IX; methods of administering chimeric and hybrid polypeptides comprising Factor IX; chimeric and hybrid polypeptides comprising Factor IX; polynucleotides encoding such chimeric and hybrid polypeptides; cells comprising such polynucleotides; and methods of producing such chimeric and hybrid polypeptides using such cells.

Abstract: This invention relates to methods for treatment of diseases of ageing including immunosenescence, immune dysfunction, inflammation and impairment of early lymphoid lineage differentiation. The invention more specifically relates to the use of granulocyte colony stimulating factors to assist in stem cell mobilization, optionally in combination with the application of a method of delivering precise magnetic field patterns which agree with the body's own natural magnetic field patterns, and further in combination with re-infusion of previously collected autologous cells and/or plasma, optionally including allogeneic (healthy donor) cells and blood plasma.

Abstract: Factor Xa variants and methods of use thereof are disclosed.

Abstract: Highly-purified soluble thrombomodulin which has a content of host cell-originated proteins being in a ratio of less than 10 ng of the proteins per 10,000 U of the soluble thrombomodulin, wherein the soluble thrombomodulin is produced by a transformant cell obtained by transfecting a host cell with a DNA containing a nucleotide sequence encoding the soluble thrombomodulin.

Abstract: The invention provides, inter alia, conjugates comprising a coagulating agent conjugated to an antibody, where the antibody specifically binds an extracellular domain epitope of a mammalian PLVAP protein. These agents specifically target HCC tumors and treat the HCC. The invention also provides methods of using these conjugates, such as methods of treating HCC by administering the conjugates provided by the invention or compositions provided by the invention, such as pharmaceutical compositions.

Abstract: The invention described herein provides new methods of preparing purified Factor VII polypeptide drug substances in large quantities (industrial scale levels) that are associated with reduced content of product-related impurities (e.g., late eluting peaks) and/or that exhibit a relatively uniform glycosylation pattern.

Abstract: The present invention relates, in general, to fibrin sealants, which contain platelet derived growth factor (PDGF) for controlled release in situ for therapeutic applications, including musculoskeletal disorders, soft tissue disorders and vascular diseases.

Abstract: A platelet aggregation inducing substance containing as an active ingredient a polypeptide having a peptide fragment represented by formula (1) (component A): -(Pro-X-Gly)n-??(1) wherein X represents Pro or Hyp; and n represents an integer of from 20 to 5,000.

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: Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and/or cell culture supernatant with a low ammonium (NH4+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.

Abstract: Described herein are method(s), kit(s), reagent(s) and the like for determining von Willebrand factor (VWF) activity in a sample in the absence of ristocetin.

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 oxidised 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: A fibrin-based hemostatic agent suitable for both civilian and military use is disclosed. The hemostatic agent comprises (i) nanoparticles to which a plurality of Knob-A recognition sequences are attached, and (ii) coiled-coils of recombinantly-produced human fibrinogen ? and chains and the ? chain globular domain. A delivery system for the hemostatic agent also is disclosed, which additionally comprises means for delivering (i) and (ii) to a wound site. The delivery means may be a CO2 canister or a shaker jet.

Abstract: Methods for producing cell lines with high levels of biologically active recombinant vitamin K dependent proteins are described. The transfected cell lines do not include heterologous genes for processing enzymes and are not subject to selection pressure such as methotrexate resistance. Cell lines producing Factor VII/VIIa and Factor IX are described. These cell lines can be used for isolation of Factor VII/VIIa and/or Factor IX for treatment of Hemophilia.

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: A method of selectively introducing a substituent into a protein proximal to a binding site on the protein for a homing peptide, comprising: (a) contacting the protein with a compound comprising a homing peptide having the ability to bind to the binding site of the protein; and (b) allowing a moiety on the protein proximal to the binding site to react with the compound comprising the homing peptide, thereby to transfer the substituent G onto the protein.

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: Provided are pro-coagulant compounds (e.g., pro-coagulant peptides or peptide derivatives) and methods of using and making those compounds. Further provided are conjugates between a pro-coagulant compound of the present disclosure (e.g., pro-coagulant peptide or peptide derivative) and a polypeptide selected from FIX, FVIIa, FVIII, and platelet targeting moieties (e.g., PDG-13), wherein the compound is linked to the polypeptide optionally via a linker. The compounds and conjugates are useful for the treatment of coagulation disorders, such as hemophilia A and hemophilia B. Further provided are methods of using and making the conjugates.

Abstract: The present invention provides a recombinant baculovirus. The baculovirus has a genome into which a gene encoding ?-glutamyl carboxylase (GGCX) and a gene encoding DT-diaphorase (NQO1) are incorporated. The present invention further provides a method for producing a recombinant vitamin K-dependent protein by using the recombinant baculovirus.

Abstract: The present invention provides a process for purifying FV starting from human plasma or a fractionation intermediate thereof, that is simple, scalable to the industrial level and relatively inexpensive compared to the methods described in the literature to date. The invention consists of the use of two anion exchange chromatography steps, the first of which has the purpose of separating the FV from the PTC component factors, while the second has the purpose of isolating the protein of interest from the majority of plasma proteins by means of selective interaction with the weak anion exchange support used. The process developed has also had a viral inactivation step and a viral removal step included, contributing to the safety of the final product obtained, without however significantly altering the process total recovery of FV, and without necessitating the introduction of additional steps for eliminating the inactivating agents used, thanks to the order in which the various steps are conducted.

Abstract: Factor VIII variants and methods of use thereof are disclosed.

Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic 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 or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

Abstract: The present invention relates to nucleic acid sequences coding for modified coagulation factors, preferably coagulation factor VIII, and their derivatives; recombinant expression vectors containing such nucleic acid sequences; host cells transformed with such recombinant expression vectors; and recombinant polypeptides and derivatives coded for by said nucleic acid sequences, whereby said recombinant polypeptides and derivatives have biological activities and prolonged in vivo half-lives compared to the unmodified wild-type proteins. The invention also relates to corresponding sequences that result in improved in vitro stability. 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 nucleic acid sequences.

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: 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: Use of a mutated antithrombin having substantially no activity, in particular no anticoagulant activity, possibly in association with an anticoagulant, for the preparation of a drug intended for the prevention or treatment of pathologies linked to or associated with coagulation disorders.

Abstract: Sequence of 55 New Found Proteins—2 new proteins in Cryoprecipitate—8 new proteins in Fraction III—8 new proteins in Prothrombin Complex Concentrate—2 new found proteins in AFCC (Fraction 33)—3 new proteins in Fraction IV and 4 new found proteins in AFOD (Fraction 42)—2 in HemoRAAS®, 3 in FibroRAAS®, 5 in GammaRAAS®, 3 in AFCC®, 1 in Fraction 3-2, 2 in Fraction 3, 4 in FibingluRAAS® (Thrombin), 3 in AFOD®, 1 in AlbuRAAS®, 1 in FibingluRAAS® (High concentrate Fibrinogen), 1 in AFCC® (From fraction IV), 2 in Transferrin from Human Plasma and their name KH1 through KH55, and 16 existing proteins in which good KH healthy cells exists and their application.

Abstract: The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic 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 or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

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 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: A platelet aggregation inducing substance containing as an active ingredient a polypeptide having a peptide fragment represented by formula (1) (component A): -(Pro-X-Gly)n-??(1) wherein X represents Pro or Hyp; and n represents an integer of from 20 to 5,000.

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: ClotFoam is a sealant and hemostatic agent for use in cases of non-compressible hemorrhage for moderate to severe bleeding. It can be applied in the operating room through laparoscopic ports, or directly over lacerated tissue in laparotomy procedures or outside the operating room through a mixing needle and/or a spray injection method following intracavitary severe trauma or surgery. Its crosslinking technology generates an adhesive scaffold that carries a fibrin sealant required for hemostasis. Clotfoam produces a foam that spreads throughout a body cavity reaching the lacerated tissue to seal tissue and promote the coagulation cascade. The composition is biocompatible and non-inflammatory. The invention uses fibrin monomer polymerized by a change of pH as active sealing component. The viscoelastic properties of the foam as well as the rapid formation of a fibrin clot ensure that the sealant remains at the site of application without being washed away by blood.

Abstract: Methods and compositions described herein relate to processes for the production of deuterated peptides, and the deuterated peptides produced accordingly. Deuterated peptides produced according to methods and compositions described herein may be produced more efficiently than such peptides produced according to prior art processes. The production process of according to methods and compositions described herein may lead to advantages in yield, purity, and/or price for deuterated peptides. Methods of marketing deuterated peptides are also disclosed.

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: The invention concerns the field of detecting and quantifying misfolded proteins/peptides. In particular the detection and quantification of misfolded proteins/peptides in body fluids, on cell surfaces of humans and mammals, the detection of misfolded proteins/peptides in reagents to be tested for scientific research and/or diagnostic use and in pharmaceutical medication or their additives and it concerns as well the removal of misfolded proteins/peptides from reagents to be tested for scientific research and/or for diagnostic purposes and from pharmaceutical medication or their additives.

Abstract: The invention concerns a concentrate of human Factor XI having high specific activity prepared using a method comprising a filtration-adsorption step and a chromatography step on cation exchange resin. The concentrate obtained is fully adapted for therapeutic use as substitution therapy in cases of Factor XI deficiency.

Abstract: The present invention provides a process for purifying FV starting from human plasma or a fractionation intermediate thereof, that is simple, scalable to the industrial level and relatively inexpensive compared to the methods described in the literature to date. The invention consists of the use of two anion exchange chromatography steps, the first of which has the purpose of separating the FV from the PTC component factors, while the second has the purpose of isolating the protein of interest from the majority of plasma proteins by means of selective interaction with the weak anion exchange support used. The process developed has also had a viral inactivation step and a viral removal step included, contributing to the safety of the final product obtained, without however significantly altering the process total recovery of FV, and without necessitating the introduction of additional steps for eliminating the inactivating agents used, thanks to the order in which the various steps are conducted.

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 therapeutic 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 or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.