Abstract: ClotFoam is an hemostatic agent designed for use in cases of non-compressible hemorrhage. It can be applied 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, or it can be used in the operating room 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, 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: The invention described herein relates to biopolymer structures. The biopolymer structures are spatially organized from the nanometer to centimeter length scales and incorporate functionally active cells. Applications of the biopolymer structures include use with stem cells.

Abstract: When genes encoding three kinds of proteins constituting fibrinogen, an ? chain (or variant of ? chain), a ? chain and a ? chain (or variant of ? chain) are incorporated into an animal cell, a constitutional ratio of respective genes is such that a ? chain (and/or variant of ? chain) gene is an equal amount to a 1000-fold amount relative to an ? chain (and/or variant of ? chain) gene and a ? chain gene and, further, by using a baculovirus P35 gene, a recombinant fibrinogen highly producing cell is prepared.

Abstract: A process for enhancing the recovery yield of proteins, especially plasma proteins, from sources containing the proteins, wherein the sources containing the proteins are frozen at temperatures of ??70° C., and the proteins from a frozen source after thawing are further processed in a per se known manner.

Abstract: The present invention is related to nucleic acids coding for adhesion factors of group B streptococcus, adhesion factors of group B streptococcus and uses thereof. More particularly, the present invention is related to a polypeptide being such adhesion factors and comprising an amino acid sequence, whereby the amino acid sequence is selected from the group comprising SEQ ID NO 11 to SEQ ID NO 20, and the use of such polypeptide for the manufacture of a vaccine.

Abstract: The present invention provides water-soluble reactive esters of carboxy polysaccharides and derivatives thereof. The reactive carboxy polysaccharide derivatives are useful per se in aqueous solutions or specifically for the formation of water-soluble covalent fibrinogen conjugates. A preferred conjugate is a hyaluronic acid-fibrinogen conjugate and fibrin adhesive, clot or matrix derived from it. Methods of preparation and methods of use in tissue repair and regeneration are also disclosed.

Abstract: The present invention is an apparatus, system and method for forming nanoscale architectures having nanoparticles bound thereto. The present invention provides a photon beam crosslinked polymer matrix, wherein the crosslinked matrix includes one or more polymers crosslinked to one or more crosslinking agents and one or more protein-coated metal nanoparticles.

Abstract: The invention relates to a method for the in vitro preparation of a synthetic multi-layer structure comprising biopolymer fibers, wherein the biopolymer fibers in each layer are unidirectionally and uniformly oriented, which comprises successive polymerisation of layers of a biopolymer fiber forming solution in the presence of a magnetic field, wherein the fiber orientation in at least one layer differs from that in at least one of its superior and/or inferior layer according to an angle alpha. The invention also relates to a biological tissue-like multi-layer structure comprising the synthetic multi-layer structure and cells inoculated therein, such as an orthogonal multi-layer collagen and/or fibrin tissue-like cornea, and the method for its preparation. The invention may be used for preventing or treating a damaged tissue, or for creating a model for biological testing, such as pharmacotoxicity testing.

Abstract: A method of concentrating proteins from whole blood comprising exposing whole blood to a covalently crosslinked hydrogel to remove water from the blood into the hydrogel to thereby concentrate the proteins in the whole blood. The hydrogel may absorb, for example, 50% or 90% of the water from the blood while excluding proteins with a weight of more than about 15,000 Daltons. In some embodiments, the hydrogels are dry, sterile, and spherical.

Abstract: Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural ? amyloid peptides (?-AP). In a preferred embodiment, the ? amyloid modulator compounds of the invention are comprised of an A? aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural ? amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural ?-AP aggregation when the natural ?-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

Abstract: Fibrinogen fusion proteins, methods of making, and methods of using fibrinogen fusion proteins are described. In a preferred embodiment the fibrinogen fusion protein contains a truncated A? chain of fibrinogen. The A? chain contains truncation site, which is a deletion of amino acids at its C-terminal region. A non-fibrinogen protein or peptide is C-terminally attached to the truncation site. The fibrinogen fusion proteins can be used alone or mixed with native fibrinogen to form fibrin polymer.

Abstract: For the separation, removal, isolation, purification, characterisation, identification or quantification of fibrinogen or a protein that is a fibrinogen analogue, an affinity adsorbent is used that is a compound of formula II wherein one X is N and the other is N, C—Cl or C—CN; Y is O, S or NR2; 0 Z is O, S or NR3; R2 and R3 are each H, alkyl, hydroxyalkyl, benzyl or &bgr;-phenylethyl; n is 0 to 6; A is a support matrix, optionally linked to the triazine ring by a spacer; R7 is a group bearing a positive charge at neutral pH; W is an optional linker; V is an aromatic group; and R8 and R9 are each H, OH, alkyl, alkoxy, amino, NH2, acyloxy, acylamino, CO2H, sulphonic acid, carbamoyl, sulphamoyl, alkylsulphonyl or halogen or a cyclic structure such as a morpholino group, or R8 and R9 are linked to form such a cyclic structure.

Abstract: The invention is directed to blood proteins produced in monocot seeds and isolated therefrom for use in therapeutic compositions, and to methods of making these isolated blood proteins and to therapeutic compositions comprising them.

Abstract: The invention provides an isolated or purified peptide that binds at least one plasma protein. In one embodiment, the isolated or purified peptide binds to fibrinogen, comprises no more than 10 amino acids, and comprises an amino acid sequence Xaa1-Xaa2-Xaa3-Xaa4-Xaa5, an amino acid sequence Gly-Xaa6-Arg-Xaa7, or an amino acid sequence selected from specific amino acid sequences provided herein. Alternatively, the isolated or purified protein binds to ?1 proteinase inhibitor and/or a protein complex comprising Apo-A1 lipoprotein and paraoxonase. The peptide comprises no more than 10 amino acids and comprises an amino acid sequence Xaa8-Xaa8-Xaa1-His-Xaa1-Xaa3, and amino acid sequence His-Xaa8-Xaa9-Xaa1-Xaa10-Xaa2, or an amino acid sequence selected from specific amino acid sequences provided herein. In addition, the invention provides isolated or purified peptide that binds to von Willebrand Factor.

Abstract: The present invention relates to a process for purifying fibrinogen, which comprises one or more process steps in which one or more contaminating proteins are depleted by negative chromatography and/or negative adsorption using cation exchanger, hydrophobic gel and/or dye gel. In addition, the invention relates to the fibrinogen which is obtained by the process of the invention and which is notable for improved stability, and to the production and use of pharmaceutical preparations comprising this fibrinogen.

Abstract: Fusion proteins containing a ligand which specifically binds to a selected vascular bed linked to an anti-thrombotic molecule are provided. Also provided are methods for use of these fusion proteins to prevent coagulation, to dissolve blood clots and to protect against the risk of iatrogenic side effects including those arising from cancer therapy and specific vascular occluding agents.

Abstract: A gene encoding a production amount-potentiating factor is introduced into an animal cell to transform the cell. Alternatively, a protein production gene and the gene encoding the production amount-potentiating factor are introduced into the animal cell to transform the cell. Herein, as the production amount potentiating factor, there is used a factor having caspase activity inhibiting activity and/or protein biosynthesis activity potentiating action, for example, baculovirus P35. Further, the animal cell is cultured by a culturing method under a condition that apoptosis is not induced, so that a protein is mass-produced.

Abstract: Using the protein chip technology, biological samples such as sera are subjected to proteome analysis. Thus, a protein which is a human fibrinogen ?-E chain decomposition product and has a molecular weight of 5,900, a protein which is an apolipoprotein AII decomposition product and has a molecular weight of 7,800, and a protein which is an apolipoprotein AI decomposition product and has a molecular weight of 28,000, each showing an increase or a decrease with the habit of drinking, are newly found out. By detecting or quantifying these proteins, a liver disease in a subject such as one having a problem of drinking can be diagnosed at the early stage.

Abstract: Described herein is a method for non-invasive detection and treatment of intra-cranial aneurysms. Antibodies are provided to specifically react/bind with antigens of the cerebral aneurism wall. The antibodies may be bound to a label and/or to a therapeutic agent for diagnosis and/or for treatment purposes thereof. Intra-cranial aneurysms are thus non-invasively detected before rupture occurs and are specifically treated.

Abstract: The blood collection, processing and transfer by separation of discrete components containing additional citrate (at least about trisodium citrate 9% w/v) in one or other of collection or processing bag provides for enhanced yield and purity of cryoprecipitate. Inhibiting the activation or denaturation of blood components including blood cells and plasma proteins and with the removal of the activated and denatured components thereby improving safety and efficacy of end products. The inventive process is particularly suited to an improved extraction process to yield concentrated clotting factors from single donors or limited pools without use of chromatography. Following extraction the remaining cryoprecipitate can advantageously be formed into a fibrin fabric used in surgeries and in the treatment of wounds.

Abstract: The invention is in the field of coagulation diagnosis and relates to a liquid, buffer-based D-dimer composition, which additionally contains fibrinogen and which is suitable as a standard material for control or calibration purposes for D-dimer test procedures.

Abstract: Treatment of implantable medical devices resistant to calcification The invention relates to a method for treating an implant comprising a protein-based substrate, including the following steps in which: (A)—the protein-based substrate is treated with a compound containing at least one aldehyde group, then (B)—the substrate is treated with a compound comprising a borohydride, then (C)—the substrate resulting from step (B) is treated with a derivative containing a silane group. The invention also relates to the treated protein-based implant obtained at the end of this method.

Abstract: Blood collection, processing and transfer leads to the separation of discrete fractions by adding additional citrate (trisodium citrate) to bring the citrate concentration to 10%-15% w/v thereby leading to enhanced yield and purity of cryoprecipitate. The improved cryoprecipitate then yields concentrated clotting factors by an improved extraction process which uses polyvinyl pyrollidone to reduce the extraction of fibrinogen.

Abstract: A process for removing viruses in fibrinogen solutions and fibrinogen obtained thereof wherein the process starts with an adjusted purified fibrinogen solution, the adjusted purified solution is frozen and then thawed at a temperature between 5 and 20° C., the undissolved materials associated with the fibrinogen are subsequently separated, the temperature is adjusted and the resultant solution is finally subjected to nanofiltration using filters having a pore size smaller than 35 nm.

Abstract: The present invention is drawn to concentrated fibrinogen compositions and associate methods and use thereof. The concentrated fibrinogen compositions can be produced by adding a sufficient amount of a cationic agent, such as protamine, to a fibrinogen containing fluid to cause the fibrinogen to form a fibrinogen precipitate; collecting the fibrinogen precipitate by a collection means, such as centrifugation; and suspending or solubilizing the fibrinogen precipitate in a liquid vehicle to form a concentrated fibrinogen composition. The concentrated fibrinogen compositions can be incorporated into systems for making fibrin glues and be used in treating wounds.

Abstract: A process for removing viruses in fibrinogen solutions and fibrinogen obtained thereof wherein the process starts with an adjusted purified fibrinogen solution, the adjusted purified solution is frozen and then thawed at a temperature between 5 and 20° C., the undissolved materials associated with the fibrinogen are subsequently separated, the temperature is adjusted and the resultant solution is finally subjected to nanofiltration using filters having a pore size smaller than 35 nm.

Abstract: The present invention relates to the identification of biomarkers for the disease condition COPD. The uses of such biomarkers in diagnosis and therapy and a novel method for their identification is are also described.

Abstract: The invention provides methods and compositions for in vivo incorporation of non-naturally encoded amino acids into polypeptides by Pseudomonas species and strains derived therefrom. Also provided are compositions including proteins with non-naturally encoded amino acids made by Pseudomonas species and strains derived therefrom.

Abstract: Process for separating proteins fibrinogen, Factor XIII and biological glue from a solubilized plasma fraction and for preparing lyophilised concentrates of said proteins Summary 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

Abstract: Proposed is a novel soluble trauma-healing and hemostatic cellulose fiber capable of absorbing and readily dissolving hemorrhaging trauma loci when applied thereto and of promoting the hemostatic action of blood platelets and fibrin and cell adhesion to the trauma site. The coagulation protein-containing soluble trauma-healing and hemostatic cellulose fiber is produced in that after treatment of a natural or regenerated cellulose fiber with an aqueous sodium hydroxide solution, said fiber is carboxymethylated by reaction with a monochloro acetic acid solution for a given time (hours) in such a manner that the degree of partial substitution of the glucose units constituting the cellulose molecule (etherification degree) is 0.5-less than 1.0% and that, furthermore, the coagulation proteins fibrinogen, thrombin, and coagulation factor XIII are imparted by surface application or chemical bonding.

Abstract: A process for manufacturing a fibrin membrane from blood plasma that was partially depleted and subjected to coagulation by adding a solution of a physiological coagulating agent, leaving the mixture to stay until forming a gelatinous blood clot, and then dehydrating said blood clot to obtain a fibrous membrane, which is subjected to washing with softening agents and then to drying until obtaining a flexible and mouldable membrane. The membrane so obtained is capable to provide an immediate and complete haemostasis, followed by a whole reabsorption, without risk of adhesions with the neighboring tissues, up to the cicatrisation of the injured tissue. The membrane is mouldable and elastic, and is provided with high mechanical properties. It may be soaked with disinfectant agents, drugs or tissue growth factors.

Abstract: The present invention provides agents for alleviating symptoms resulting from inflammation, which have an activity to alleviate inflammatory symptoms caused by bacterial infection, particularly accumulation of body fluid such as bronchocavemous plasma exudation, ascites, etc., at the inflammatory site, or excessive increase of blood neutrophils; symptoms resulting from inflammation caused by bacterial infection, particularly accumulation of body fluid such as bronchocavemous plasma exudation ascites, etc., at the inflammatory site, or excessive increase of blood neutrophils, can be alleviated effectively by ingesting or administering orally or parenterally a composition containing human-type lactoferrin as an effective component.

Abstract: A stable blood factor composition contains a stabilising amount of trehalose in the absence of human serum albumin to provide a product stable at up to 60° C.

Abstract: Proteinaceous gels having visualization agents and methods of use thereof are disclosed herein. Further, polymeric crosslinking agents are disclosed that have an inert water soluble polymeric component, biodegradable components, functional components reactive with chemical groups on a protein, for example, amine or thiol groups. The inert polymeric component may be flanked at each end with a biodegradable component which is flanked at each end with a protein reactive functional component. A polymeric crosslinking agent is disclosed having a biodegradable component, polyalkylene oxide, and at least three reactive functional groups that are each capable of forming a covalent bond in water with at least one functional group such as an amine, thiol, or carboxylic acid.

Abstract: The present invention provides a method for the part purification of fibrinogen from milk, the method comprising the transfer of protease enzyme which is present in the milk, into the whey phase with the removal or partition if fibrinogen into another phase of the milk. The present invention also provides a method for obtaining fibrinogen from a fluid, the method comprising: a) contacting the fluid with a hydrophobic interaction chromatography resin under conditions where the fibrinogen binds to the resin; and b) removing the bound protein by means of elution.

Abstract: Use of factor XIII for inhibiting the formation of seromas by administering factor XIII. The factor XIII can be administered locally at the site of a wound or surgery or administered systemically. If the factor XIII is administered locally, it can be activated or non-activated and may be administered in conjunction with activated thrombin.

Abstract: We disclose haptotactic peptides having sequences homologous to specific portions of the carboxy terminal sequence of fibrinogen chains. The peptides derived from fibrinogen pre-C? chain possess activities of cell attraction or cell attachment to a surface to which the peptide is covalently bound.

Abstract: This invention provides an imaging agent which comprises a polypeptide labeled with an imageable marker, such polypeptide having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin. The invention further provides a method wherein the imaging agent is used for imaging a fibrin-containing substance, i.e., a thrombus or atherosclerotic plaque. Further provided are plasmids for expression of polypeptides having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin, hosts containing these plasmids, methods of producing the polypeptides, methods of treatment using the polypeptides, and methods of recovering, refolding and reoxidizing the polypeptides.

Abstract: The present invention relates to a novel storage-stable formulation for fibrinogen in liquid or viscous liquid form comprising divalent metal ions. The fibrinogen formulation may comprise other conventional formulation ingredients and particularly preferably comprises a complexing agent. The invention further relates to the production and use of the fibrinogen formulation of the invention.

Abstract: The instant invention involves the use of a combination of preparatory steps in conjunction with mass spectroscopy and time-of-flight detection procedures to maximize the diversity of biopolymers which are verifiable within a particular sample. The cohort of biopolymers verified within such a sample is then viewed with reference to their ability to evidence at least particular disease state; thereby enabling a diagnostician to gain the ability to characterize either the presence or absence of at least one disease state relative to recognition of the presence and/or the absence of the biopolymer.

Abstract: Biocompatible crosslinked polymers, and methods for their preparation and use, are disclosed in which the biocompatible crosslinked polymers are formed from water soluble precursors having electrophilic and nucleophilic functional groups capable of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable or not are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body. Applications for such biocompatible crosslinked polymers and their precursors include controlled delivery of drugs, prevention of post-operative adhesions, coating of medical devices such as vascular grafts, wound dressings and surgical sealants. Visualization agents may be included with the crosslinked polymers.

Abstract: The present invention pertains to a pharmaceutical conjugate comprising an insoluble carrier to which first and second active agents are bound, respectively via a first linker to a first functional group on the carrier and via a second linker to a second functional group on the carrier. For example, fibrinogen and Factor VIII can be independently linked to albumin microcapsules.

Abstract: This invention describes a bioerodible fibrin material which is obtained by mixing fibrinogen and thrombin reconstituted or diluted with a particular high tonic strength medium, free of calcium. Such a fibrin-based biomaterial develops a tight structure with thin fibers and small pore size suitable for use as an anti-adhesion barrier. In this invention, thrombin is no longer the variable which governs the tightness and the porosity of the fibrin material obtained, but still controls the clotting time. The mechanical behavior, high-water capacity, and releasable retention properties for therapeutic agents of this fibrin structure causes the fibrin material to be ideally suited for use as a drug delivery device, capable of delivering proteins, hormones, enzymes, antibiotics, antineoplastic agents and even cells for local and systemic treatment of human and non-human patients.

Abstract: The present invention relates to methods for purifying fibrinogen. In one aspect, the present invention relates to a method of separating fibrinogen from plasma fraction I precipitate. In another aspect, the invention relates to the purification of fibrinogen using ion exchange chromatography.

Abstract: Use of fibrinogen multimers having at least 6 fibrinogen units as an ingredient for a fibrin sealant.

Abstract: The instant invention involves the use of a combination of preparatory steps in conjunction with mass spectroscopy and time-of-flight detection procedures to maximize the diversity of biopolymers which are verifiable within a particular sample. The cohort of biopolymers verified within such a sample is then viewed with reference to their ability to evidence at least particular disease state; thereby enabling a diagnostician to gain the ability to characterize either the presence or absence of at least one disease state relative to recognition of the presence and/or the absence of the biopolymer.

Abstract: Use of factor XIII for inhibiting the formation of seromas by administering factor XIII. The factor XIII can be administered locally at the site of a wound or surgery or administered systemically. If the factor XIII is administered locally, it can be activated or non-activated and may be administered in conjunction with activated thrombin.

Abstract: This invention provides supplemented tissue sealants, methods for their production and use thereof. Disclosed are tissue sealants supplemented with at least one cytotoxin or cell proliferation inhibiting composition. The composition may be further supplemented with, for example, one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, cytokines, drugs, growth factors, interferons, hormones, lipids, deminearlized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like.

Abstract: This invention provides methods for the localized delivery of supplemented tissue sealants, wherein the supplemented tissue sealants comprise at least one composition which is selected from one or more antibodies, analgesics, anticoagulants, anti-inflammatory compounds, antimicrobial compositions, antiproliferatives, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Further provided are methods of using the site-specific supplemented tissue sealants, including preparation of a biomaterial.

Abstract: This invention provides a fibrin sealant dressing, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, antiinflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and/or using the unsupplemented or supplemented fibrin sealant dressing.