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: Methods for treating diseased or injured tissue by implanting into the tissue at a site of the disease or injury a porous freeze-dried fibrin matrix formed from plasma proteins. The proteins include fibrinogen cleaved by the action of thrombin at varying concentrations sufficient to cleave the fibrinogen and Factor XIII. The matrix has less than 10% residual moisture and is devoid of exogenous anti-fibrinolytic agents, plasminogen and of organic chelating agents. Alternatively, the plasma proteins comprise partially purified plasma proteins that are devoid of plasminogen.

Abstract: The present invention provides, inter alia, transgenic non-human animals, such as transgenic mice. The animals contain in their genome a polynucleotide encoding a von Willebrand factor (VWF) polypeptide, which polypeptide forms a thrombus when in the presence of human platelets. Nucleic acid sequences and vectors for generating the transgenic non-human animals, and methods for using the transgenic non-human animals are provided as well. Chimeric VWF proteins are also provided.

Abstract: The present invention aims to provide methods to detect cognitive impairment including mild cognitive impairment and Alzheimer disease by using a protein or its partial peptide that differs in presence or absence, or in quantity between non-cognitive impairment and patients with cognitive impairment and further aims to present biomarkers comprising said protein and said partial peptide to be used to detect cognitive impairment including Alzheimer disease or mild cognitive impairment. Specifically, a biomarker for diagnosis of psychiatry disease or cognitive impairment comprising protein fragment or peptide of not less than 5 amino acid residues arising from at least one protein or peptide selected from the group of proteins consisting of amino acid sequence expressed by SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, and 25 and selected from the group of partial peptide in these proteins consisting of amino acid sequence expressed by SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, and 27.

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: The present invention relates to a method for capturing virus-like particles of interest from a mixture comprising the use of an expanded bed of adsorbent; suitably wherein said method comprises the steps of: (a) providing an expanded bed of adsorbent; (b) contacting the mixture with the adsorbent such that the constituents of the mixture contact the expanded bed of adsorbent; (c) optionally washing the adsorbent; and (d) optionally eluting the particle of interest from the adsorbent.

Abstract: The invention relates to a method for extracting a protein from milk, having at least one hydrophobic pocket and a negative charge to the natural pH of milk, that comprises the following steps: a) skimming and delipidation of the milk; b) passing the delipidated and skimmed fraction containing the protein on a chromatographic substrate on which is grafted a ligand having both a hydrophobic characteristic and an ionic characteristic in pH conditions enabling the protein to be retained on the substrate, the pH being higher than 4.6; c) elution of the protein; d) purification of the eluted fraction by removing the milk proteins from the eluted fraction; and e) recovering the protein.

Abstract: The present invention provides conjugates encompassed by the following structure, wherein: D is a residue of an active agent bearing at least one amino group; and PEG-m is a methoxy end-capped poly(ethylene glycol), and further wherein the active agent is a coagulation factor having a molecular weight of greater than 100 kDa. Methods of making conjugates, and methods for administering conjugates, are also provided.

Abstract: The present invention is directed to particular monoclonal antibodies and fragments thereof that find use in the detection, prevention and treatment of influenza virus infections. In particular, these antibodies may neutralize or limit the replication of influenza virus. Also disclosed are improved methods for producing such monoclonal antibodies, including novel immunogens for use in vaccination and production of protective immune responses.

Abstract: A peptide or peptide derivative comprising: (i) WDLYFEIVW (SEQ ID NO: 1); or (ii) a variant amino acid sequence comprising one, two, three or four L-amino acid substitutions in WDLYFEIVW (SEQ ID NO: 1); or (iii) the retro-inverso variant of the peptide or peptide derivative of either one of parts (i) and (ii), wherein said peptide or peptide derivative has procoagulant activity. A peptide or peptide derivative comprising: (i) an amino acid sequence comprising imfwydcye; or (ii) a variant amino acid sequence comprising one, two, three, four, five or six amino acid substitutions in imfwydcye, wherein said peptide or peptide derivative has procoagulant activity.

Abstract: The invention includes a heparin activated Antithrombin III encapsulated into a sterically stabilized anti-HLA-DR immunoliposome for the treatment of HIV infection in a human patient.

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: Compositions and methods for targeting substances to fibrinogen, fibrin monomers, or fibrin polymers are provided. These compositions and methods generally involve the use of fibrin knob peptides that bind fibrin(ogen), which can be used to detect fibrin(ogen) and modulate fibrin polymerization and fibrinolysis.

Abstract: The present invention provides Factor IX moiety-polymer conjugates having a releasable linkage. Methods of making conjugates, methods for administering conjugates, are also provided.

Abstract: The invention relates to the field of glycoprotein processing in transgenic plants used as cost efficient and contamination safe factories for the production of recombinant biopharmaceutical proteins or pharmaceutical compositions comprising these glycoproteins. The invention provides a plant comprising a functional mammalian enzyme providing mammalian GnTIII that is normally not present in plants, said plant additionally comprising at least a second mammalian protein or functional fragment thereof that is normally not present in plants.

Abstract: The invention relates to a method for extracting a protein from milk, having at least one hydrophobic pocket and a negative charge to the natural pH of milk, that comprises the following steps: a) skimming and delipidation of the milk; b) passing the delipidated and skimmed fraction containing the protein on a chromatographic substrate on which is grafted a ligand having both a hydrophobic characteristic and an ionic characteristic in pH conditions enabling the protein to be retained on the substrate, the pH being higher than 4.6; c) elution of the protein; d) purification of the eluted fraction by removing the milk proteins from the eluted fraction; and e) recovering the protein.

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: Methods for the treatment of coagulation disorders using Factor V/Va variants are provided.

Abstract: A liquid aqueous composition comprising (i) a factor VII polypeptide; (ii) an agent suitable for keeping pH in the range of from about 4.0 to about 8.0; (iii) an agent selected from the list of: a calcium salt, a magnesium salt, or a mixture thereof; wherein the concentration of (iii) is at least 15 mM is described.

Abstract: A method for purifying GLA-domain coagulation proteins, includes the following steps: a) bringing a sample containing one or more GLA-domain coagulation proteins into contact with an affinity substrate on which nucleic aptamers which bind specifically to the GLA-domain coagulation proteins are immobilized, in order to form complexes between (i) the nucleic aptamers and (ii) the GLA-domain coagulation protein(s), b) releasing the GLA-domain coagulation protein(s) from the complexes formed in step a), and c) recovering the GLA-domain coagulation protein(s) in a purified form.

Abstract: A biomarker, method, test kit, and diagnostic system for detecting the presence of lymphoma in a person are disclosed. The lymphoma may be Hodgkin's lymphoma or non-Hodgkin's lymphoma. The person may be a high-risk subject. In one embodiment, a plasma sample from a person is obtained. The level of at least one protein listed in Table S3 in the plasma sample is measured. The level of at least one protein in the plasma sample is compared with the level in a normal or healthy subject. The lymphoma is diagnosed based upon the level of the at least one protein in the plasma sample in comparison to the normal or healthy level.

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor X and 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 reversing anticoagulation, stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

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: A process of manufacturing a prion-free Vitamin K dependent Protein in a purification sequence employing chromatography characterized in that at least one chromatography step is performed using a multimodal resin providing a fraction containing Vitamin K dependent Protein in an aqueous solution; contacting the fraction containing the Vitamin K dependent Protein with a multimodal resin at a pH between 6-9; optionally washing the multimodal resin having the Vitamin K dependent Protein adsorbed with an aqueous washing buffer to wash away contaminants and retain the Vitamin K dependent Protein, before the Vitamin K dependent Protein is eluted; the Vitamin K dependent Protein is eluting from the multimodal resin at a pH between 6 to 9 in a buffer comprising arginine; and optionally collecting Vitamin K dependent Protein containing fractions in purified or enriched form.

Abstract: The application is based on the surprising finding that proteins regulated by increased c-myc activity in the liver can be used as sis and/or treatment monitoring of cancer and dysplasia, in particular of liver cell dysplasia and hepatocellular carcinoma (HCC), and wherein the proteins are selected from a first group consisting of Polymeric immunoglobulin receptor, Phosphatidylinositol—glycan—specific phospholipase D, Alpha—fetoprotein, Antithrombin 3, Apolipoprotein E, Apolipoprotein M, Fibrinogen beta-chain, Haptoglobin, Paraoxonase 1, Retinol binding protein, Serum amyloid P- component, Transthyretin, or from a second group consisting of Afamin, Glutathione peroxidase 3, Hemopexin, Major urinary protein, Serine protease inhibitor A3K. Consequently, medical uses of said proteins, of corresponding compositions, of corresponding antibodies, of corresponding siRNA and of corresponding nucleotide sequences are claimed. Also claimed are corresponding kits and corresponding methods and procedures.

Abstract: The invention relates to a method for purifying a factor XIII polypeptide from a biological material, the method comprising subjecting the material to sequential chromatography on an anion-exchange matrix and a hydrophobic interaction matrix.

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 chimeric therapeutic polypeptide of a pre-existing therapeutic polypeptide is disclosed, as are a method of enhancing folded stabilization and a pharmaceutical composition of the glycosylated chimer. The pre-existing and chimeric polypeptides have substantially the same length, substantially the same amino acid residue sequence, and exhibit at least one tight turn containing a sequence of four to about seven amino acid residues in which at least two amino acid side chains extend on the same side of the tight turn and are within less than about 7 ? of each other. The chimeric therapeutic polypeptide has the sequon Aro-(Xxx)n-(Zzz)p-Asn-Yyy-Thr/Ser (SEQ ID NO:001) within that tight turn sequence such that the side chains of the Aro, Asn and Thr/Ser amino acid residues project on the same side of the turn and are within less than about 7 ? of each other. That sequon is absent from the pre-existing therapeutic polypeptide.

Abstract: A hemostatic agent designed for use in cases of non-compressible hemorrhage. It can be applied through a mixing needle and/or a spray injection method following abdominal, chest, extremities or other intracavitary severe trauma to promote hemostasis, or it can be used for laparoscopic procedures or other surgical procedures in which compression is not possible or recommended. Its crosslinking technology generates an adhesive three-dimensional polymeric network or scaffold that carries a fibrin sealant required for hemostasis. When mixed, it produces a foam that spreads throughout a body cavity reaching the lacerated tissue to seal tissue and promote the coagulation cascade. The fibrin components are produced by a novel dialysis method which does not present thrombin to the immune system and can be maintained in solution for six weeks without significant proteolytic degradation.

Abstract: Therapeutic agents suitable for use as artificial platelets are described. The agents comprise a fibrinogen binding precursor bound to an insoluble carrier, wherein the fibrinogen binding precursor can be converted by a wound site specific agent, such as thrombin, to a fibrinogen binding component bound to the carrier. The fibrinogen binding component has increased ability to bind fibrinogen compared to the fibrinogen binding precursor. The agents may be used to treat patients with deficiencies in their own platelets, such as hereditary or acquired defects of platelet numbers (thrombocytopenia) or function (thrombasthenia).

Abstract: The present invention relates to a modified and optimized Factor VIII or Factor IX nucleic acid for inclusion in a chimeric virus vector. Use of such vector can be used for treatment of hemophilia.

Abstract: The present invention relates to new IL-17 inhibiting polypeptides, corresponding fusion proteins, compositions and medical uses thereof.

Abstract: The present invention relates to modified therapeutic proteins, such as e.g. coagula-tion factors. In particular, the present invention relates to conjugated Factor VIII molecules such as e.g. FVII, FVIII, or FIX comprising a hydrophobic side group.

Abstract: The present disclosure relates to materials and methods of conjugating a water soluble polymer to a therapeutic protein.

Abstract: The invention relates to the field of the diagnosis of and vaccination against Streptococcal infections, and to the detection of virulence markers of Streptococci. The invention discloses a method for modulating virulence of a Streptococcus comprising modifying a genomic fragment of the Streptococcus, wherein the genomic fragment comprises at least a functional part of a fragment identifiable by hybridization in Streptococcus suis to a nucleic acid or fragment thereof.

Abstract: Disclosed herein are cell penetrating peptides useful as treatment for Human Immunodeficiency Virus.

Abstract: Methods and kits for measuring levels of von Willebrand factor function in a sample without using a platelet aggregation agonist, such as ristocetin, comprising recombinant glycoprotein Ib? having at least two of a G233V, D235Y and M239V mutations and an agent to detect a complex between the recombinant glycoprotein Ib? and von Willebrand factor.

Abstract: ClotFoam is a surgical sealant and hemostatic agent designed to be used in cases of non-compressible hemorrhage. 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 abdominal, chest, extremities or other intracavitary severe trauma to promote hemostasis. Its crosslinking technology generates an adhesive three-dimensional polymeric network or scaffold that carries a fibrin sealant required for hemostasis. When mixed, Clotfoam produces a foam that spreads throughout a body cavity reaching the lacerated tissue to seal tissue and promote the coagulation cascade. The viscoelastic attachment properties of the foam as well as the rapid formation of a fibrin clot that ensure that the sealant remains at the site of application without being washed away by blood or displaced by movement of the target tissue.

Abstract: A method for purifying biologically active GLA-domain coagulation proteins, includes the following steps: a) bringing a sample that contains one or more GLA-domain coagulation proteins and may contain biologically inactive molecules of GLA-domain protein(s), into contact with an affinity substrate on which nucleic aptamers that bind specifically to at least one biologically active GLA-domain coagulation protein are immobilized, in order to form complexes between (i) the nucleic aptamers and (ii) the GLA-domain coagulation protein(s), b) releasing the GLA-domain coagulation protein(s) from the complexes formed in step a), and c) recovering the biologically active GLA-domain coagulation protein(s) in a purified form.

Abstract: Methods of harvesting proteins directly from bioreactors to avoid at several steps in the purification of recombinant drugs are disclosed.

Abstract: Disclosed are biologically active protein conjugates that comprise a biologically active polypeptide coupled via a peptide bond to a polypeptide comprising from 2 to about 500 units of a repeating peptide motif, wherein the biologically active protein conjugate exhibits a modified plasma half-life compared to the intrinsic half-life of the unconjugated biologically active polypeptide or protein. Also disclosed are methods of making and using the conjugated proteins, as well as methods for determining whether a given conjugate exhibits a modified half life relative to the intrinsic half life of the unconjugated polypeptide.

Abstract: The present invention is directed to a hemostatic textile, comprising: a material comprising a combination of glass fibers and one or more secondary fibers selected from the group consisting of silk fibers; ceramic fibers; raw or regenerated bamboo fibers; cotton fibers; rayon fibers; linen fibers; ramie fibers; jute fibers; sisal fibers; flax fibers; soybean fibers; corn fibers; hemp fibers; lyocel fibers; wool; lactide and/or glycolide polymers; lactide/glycolide copolymers; silicate fibers; polyamide fibers; feldspar fibers; zeolite fibers, zeolite-containing fibers, acetate fibers; and combinations thereof; the hemostatic textile capable of activating hemostatic systems in the body when applied to a wound. Additional cofactors such as thrombin and hemostatic agents such as RL platelets, RL blood cells; fibrin, fibrinogen, and combinations thereof may also be incorporated into the textile. The invention is also directed to methods of producing the textile, and methods of using the textile to stop bleeding.

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 present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.

Abstract: Methods for the treatment of coagulation disorders using Factor V/Va variants are provided.

Abstract: Disclosed are methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, disclosed are assays that detect one or more markers selected from the group consisting of Prostatic acid phosphatase, Lactotransfenin, Soluble erythropoietin receptor, Von Willebrand factor, Soluble endothelial protein C receptor, and Beta-2-glycoprotein 1 as diagnostic and prognostic biomarkers in renal injuries.

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: Techniques to glycosylation are described, and more particularly to the production of glycosylation structures that are resistant to enzymatic degradation, thereby modulating one or more of their biological properties or those of therapeutic moieties incorporating them, and in particular to reacting activated carbohydrate substrates containing fluorine, such as 3-fluoro sialic acid compounds, with sugar acceptors to produce covalent conjugates of the sugar acceptor and one or more of the sialic acid compounds.

Abstract: The invention relates to fusion proteins that bind the enzyme thrombin and enhance the activation of the substrate Factor VII to the product Factor VIIa. The invention is also directed to polynucleotides, vectors, host cells, pharmaceutical compositions, and methods of treatment.

Abstract: The current invention relates to procoagulant fusion proteins, polynucleotides that encode said fusion proteins and cells that expresses said fusion proteins. Furthermore, the current invention relates to fusion proteins for use as a medicament. Individuals that have a coagulopathy, such as haemophilia A and B with or without inhibitors, may be treated with fusions proteins of the current invention.