Abstract: The invention is based on the surprising finding that proteins regulated by excessive EGFR signalling in the liver may be used as biomarkers in the diagnosis, prognosis and/or monitoring of treatment of diseases, including liver cell dysplasia or hepatocellular carcinoma (HCC), wherein the protein is selected from a first group consisting of Arginase type II, 4931406C07Rik (Ester hydrolase C11orf54 homolog), Akr1c12 protein, Alanyl-tRNA synthetase, Aldo-keto reductase family 1 member C14, Aldo-keto reductase family 1 member C6, Aldolase 3, Alpha glucosidase 2, Beta 5-tubulin, Cai protein (Pdia4), cDNA sequence BC021917 (dihydroxyacetone kinase 2 homolog), Farnesyl diphosphate synthetase, Fatty acid binding protein 5 epidermal, Inosine triphosphatase, Interleukin 25, Kininogen 1, LIM and SH3 protein 1, Major vault protein, Nucb1 protein, Poly(rC) binding protein 2; heterogeneous nuclear ribonucleoprotein X, Psmd11 protein, RIKEN cDNA 2410004H02, Rps12 protein, Sars1 protein, Sorcin, T43799 proteasome protein p

Abstract: The present invention provides methods for separating proteins from a protein mixture. In one aspect, a method for separating a high concentration protein mixture into a bound protein fraction and a flow-through protein fraction can include delivering a protein mixture through an ion exchange column at a fixed pH and a fixed salt concentration. The fixed pH and the fixed salt concentration have been preselected to cause separation of the protein mixture into a bound protein fraction and a flow-through protein fraction. In this case, the bound protein fraction binds to the ion exchange column and the flow-though protein fraction flows though the ion exchange column. The method can further include receiving the flow-through protein fraction from the ion exchange column separate from the bound protein fraction, wherein either the bound protein fraction or the flow-through fraction contains a protein of interest.

Abstract: Compositions for forming a self-reinforcing composite biomatrix, methods of manufacture and use therefore are herein disclosed. Kits including delivery devices suitable for delivering the compositions are also disclosed. In some embodiments, the composition can include at least three components. In one embodiment, a first component can include a first functionalized polymer, a second component can include a second functionalized polymer and a third component can include silk protein or constituents thereof. In some embodiments, the composition can include at least one cell type and/or at least one growth factor. In some embodiments, the composition can include a biologic encapsulated, suspended, disposed within or loaded into a biodegradable carrier. In some embodiments, the composition(s) of the present invention can be delivered by a dual lumen injection device to a treatment area in situ, in vivo, as well as ex vivo applications.

Abstract: Compositions for forming a self-reinforcing composite biomatrix, methods of manufacture and use therefore are herein disclosed. Kits including delivery devices suitable for delivering the compositions are also disclosed. In some embodiments, the composition can include at least three components. In one embodiment, a first component can include a first functionalized polymer, a second component can include a second functionalized polymer and a third component can include silk protein or constituents thereof. In some embodiments, the composition can include at least one cell type and/or at least one growth factor. In some embodiments, the composition can include a biologic encapsulated, suspended, disposed within or loaded into a biodegradable carrier. In some embodiments, the composition(s) of the present invention can be delivered by a dual lumen injection device to a treatment area in situ, in vivo, as well as ex vivo applications.

Abstract: The invention discloses a method for the production of a polymerized product comprising the following steps: providing a polymerization device to which a polymerization mixture and a separation medium can be applied and wherein flow of said mixture and medium can be conducted in appropriate ducts for said mixture and medium, transporting said polymerization mixture in a duct of said polymerization device thereby allowing the polymerization reaction, transporting said mixture in a duct of said polymerization device in a continuous flow, interrupting said continuous flow of said mixture with said separation medium so as to obtain consecutive volumes of said mixture and volumes of said separation medium, further transporting said consecutive volumes of said mixture and volumes of said separation medium in a duct of said polymerization device wherein said mixture further polymerizes to obtain a discontinuous polymerized product, and removing said discontinuous polymerized product from said polymerization devi

Abstract: The present invention provides improved methods for the purification of factor XIII. In particular, the methods provide compositions containing 5% or less contaminating proteins. In particular embodiments of the present invention the methods provide purified factor XIII compositions comprising less than 1% activated factor XIII, less than 2% protein aggregates, and/or less than 5% charge isomers of factor XIII. The methods do not require the use a precipitation or crystallization step common to prior methods of isolating factor XIII. Instead, the method uses immobilized metal affinity chromatography to remove various contaminants common to recombinant expression of factor XIII. Further, a combination of various chromatography methods including ion exchange chromatography, hydrophobic affinity chromatography, and immobilized metal affinity chromatography comprise a simple and less expensive method to produce a pharmaceutical grade factor XIII product at high yield.

Abstract: An objective of the invention is to provide an adsorbent allowing purification of a blood coagulation factor or a cell adhesion factor under mild conditions, according to simple procedures, and at a low cost and safely while having a high affinity and a high resistance to deterioration, and a method for purifying the blood coagulation factor or the cell adhesion factor; a solution is to apply a polypeptide having peptide fragments represented by formula (1) as the adsorbent for the blood coagulation factor or the cell adhesion factor, and to purify the blood coagulation factor or the cell adhesion factor using the adsorbent: -(Pro-Hyp-Gly)n- Wherein, in formula (1), n is an integer from 2 to 9,000.

Abstract: A method for changing conformation of globular proteins is provided. The method controls the concentration of the globular proteins and the adsorption time of the globular proteins from the aqueous solution to the air/liquid interface, so that the main conformation of the globular proteins in a protein monolayer can be changed into ?-sheet or ?-helix. Meanwhile, the protein monolayer having the conformation of ?-sheet or ?-helix can be vertically deposited and transferred onto a substrate for various applications according to needs. The present invention can change three-dimensional structures of biological molecules and remain original functions thereof without additionally using any physical/chemical treatment to change the conformation of the globular proteins.

Abstract: The present invention relates to fibronectin based scaffold domain proteins that bind PCSK9. The invention also relates to the use of the innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol related diseases. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative protein.

Abstract: The invention relates to the production of recombinant human fibrinogen (rhFib) in the milk of transgenic mammalian animals. This production and subsequent purification process is generally hampered by the occurrence of so-called ‘clots’ and ‘flakes’ in the milk which, in severe cases, may prevent the cow from being milked at all, resulting in a halt of lactation. These clots and flakes occur because of the expression of the fibrinogen protein, which is a factor that is normally involved in blood clotting. The invention relates to solving this milk clotting problem by treating the (lactating) animals with anticoagulants such as coumarins. A preferred anticoagulant that is used in the methods of the present invention is warfarin.

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 fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.

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: The present invention relates to fibrinogen preparations enriched in ?-extended fibrinogen. Compositions comprising such preparations show improved clotting properties compared to preparations based on HMW Fib which typically contain no or only low amounts of ?-extended fibrinogen. In particular, clot formation time and the clot strength of a clot made by ?-extended fibrinogen are improved. In addition, plasmin-mediated degradation of ?-extended fibrinogen is reduced as compared to plasma derived fibrinogen.

Abstract: The invention relates to purification of an intact, non-degraded macromolecule from a biological mixture comprising the macromolecule in the presence of its lytic enzyme. The method comprises providing the biological mixture as a heterogeneous mixture comprising the lytic enzyme, at least partially, in soluble form and the macromolecule, at least partially, in non-soluble form; batch-wise contacting the heterogeneous mixture with an immobilized inhibitor of the lytic enzyme; increasing the solubility of the macromolecule in the mixture; and removing the immobilized inhibitor from the mixture.

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 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: A composition including a peptide sequence of the formula ?X1-X2, the peptide sequence corresponding to an amino acid sequence of a fibrin beta chain fragment of a Bbeta chain of fibrinogen, wherein X1 represents an N-terminal end of the peptide sequence, and X2 represents a C-terminal end of the peptide sequence, wherein the peptide sequence includes additional amino acids between X1 and X2, wherein the peptide sequence may contain a non-naturally occurring amino acid residue, wherein the peptide sequence is other than a wild-type ?15-42 monomer sequence per se, and wherein the peptide sequence is other than (?15-66)2 dimer having two chains with each chain limited to wild type amino acids ?15-65 and each chain further including a non-naturally occurring Gly at position 66 of each chain. Methods for treatment and pharmaceutical combinations may include a polypeptide agent such as Thymosin beta 4.

Abstract: Bioactive molecules are entrapped within a matrix for the controlled delivery of these compounds for therapeutic healing applications. The matrix may be formed of natural or synthetic compounds. The primary method of entrapment of the bioactive molecule is through precipitation of the bioactive molecule during gelation of the matrix, either in vitro or in vivo. The bioactive molecule may be modified to reduce its effective solubility in the matrix to retain it more effectively within the matrix, such as through the deglycosylation of members within the cystine knot growth factor superfamily and particularly within the TGF? superfamily. The matrix may be modified to include sites with binding affinity for different bioactive molecules, for example, for heparin binding.

Abstract: A protein scaffold based on a consensus sequence of the tenth fibronectin type III (FN3) repeat from human fibronectin, including isolated nucleic acids that encode a protein scaffold, vectors, host cells, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices. In particular, protein scaffold molecules binding to IgG based on the consensus sequence have been identified as useful for diagnostic and/or therapeutic applications.

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

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: Biocompatible phase invertible proteinaceous compositions and methods for making and using the same are provided. Phase invertible compositions in accordance with the invention are prepared by combining a liquid proteinaceous substrate and a liquid crosslinking composition, where the liquid crosslinking composition includes a macromolecular crosslinking agent. Also provided are kits for use in preparing the subject compositions. The subject compositions, kits and systems find use in a variety of different applications.

Abstract: Fibrin sealant (FIBRINGLURAAS®) consisting of a kit of lyophilized high concentrate fribinogen intentionally enriched and preserved with fibronolysis inhibitor A1AT, either non-heated or heating to at least 1° C. and above, preferably at least 101° C., and lyophilized thrombin used to compound glue membrane, the diameter of which is less than 10 micrometers the actual size of the glue membrane of the fibrin sealant (FIBRINGLURAAS®) is from 0.6 ?m, to 101° C. heating 0.005 micrometers. Thrombin, a protein, contains good healthy cells. High concentrate fibrinogen, another protein, contains good healthy cells. AFOD (HDL ApoA1), another protein, contains good healthy cells and its topical applications for all solid tumor cancers.

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 discloses a novel application of fibrinogen-420 and its active domain (alpha EC domain), and a separate alpha EC domain protein has the same or similar function with fibrinogen-420. Fibrinogen-420 and its active domain can be widely used in inhibiting protein aggregation, helping protein refolding, drugs which can prevent and/or treat protein conformation disease, detecting denatured protein in quality control and protect protein from denaturation.

Abstract: Provided are novel post-translationally modified variants of fibrinogen, in particular human fibrinogen, a method for producing and isolating said variants, as well as methods of using the variant, in particular in systemic and local/topical treatment and prophylaxis of excessive bleeding.

Abstract: The subject invention provides novel devices and methods for the detection of the presence and/or activity of proteases in biological samples

Abstract: A plasma coating device for treating a wound comprises a plasma chamber having: one or more electrodes, a gas supply inlet, a plasma outlet exposed to ambient pressure, and an ignition system operatively connected to the electrodes for providing a non-thermal equilibrium plasma within the plasma chamber. An aerosol delivery system is operable to introduce a bioresorbable material as an aerosol into the plasma, to produce a coating on the wound surface.

Abstract: The structural design, preparative methods and chemical composition of two structural formulations of bivalent vaccines against morphine-heroin addiction (morphine-6-hemisuccinyl-EDC-TFCS-tetanus toxoid and 3-O-carboxymethylmorphine-EDC-TFCS-tetanus toxoid), are disclosed. These vaccines are suitable for human use in which they are capable of triggering the synthesis of polyclonal antibodies against morphine opiate and its structural analogue, heroin, through the repeated in vivo administration of these formulations, in active vaccination protocols, in pre-clinical studies in rodents. The active vaccination paradigm through which these immunogens trigger a humoral immune response consolidated with a long-term immunological memory, characterized by the presence of high titers of specific antibodies against these two drugs of abuse, is also disclosed.

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: There is provided compositions-of-matter comprising fibrin or fibrinogen crosslinked with at least one reducing sugar.

Abstract: The invention concerns the method of production of a polyanionic macromolecule which is a protein built, among others, form polar amino acids (such as lysine, arginine, aspartic acid, glutamic acid), characteristic in that, that as a result of the reaction between amine groups and the cyclic anhydride of dicarboxylic acid, the charge changes towards more negatively charged carrier. This reaction gives rise to better therapeutic properties of macromolecules modified in this way.

Abstract: A method of crosslinking a protein or peptide for use as a biomaterial, the method comprising the step of irradiating a photoactivatable metal-ligand complex and an electron acceptor in the presence of the protein or peptide, thereby initiating a crosslinking reaction to form a 3-dimensional matrix of the biomaterial.

Abstract: Using the Sup35 prion proteins of two distantly related yeast species, it is established that prion replication is initiated by small elements of primary sequence, which can be identified using arrays of short peptides. Subtle differences in replication elements govern the formation of distinct aggregate conformations (prion strains) and also determine their species-specific seeding activities. A Sup35 chimera that promiscuously forms prions in more than one species does so by virtue of carrying the replication element of each species. Mutations or conditions that cause the chimera to assemble into distinct prion strains favor recognition of distinct replication elements. Therefore, subtle differences in small sequences that constitute prion replication elements encode important determinants of prion propagation and transmission.

Abstract: The invention relates to a chimeric monomer-dimer hybrid protein wherein said protein comprises a first and a second polypeptide chain, said first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and said second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

Abstract: The present invention relates to nucleotide sequences encoding a fibrinogen alpha, beta or gamma chain. The sequences are optimized for expression in a eukaryotic cell culture system. Such optimized nucleotide sequences allow for the efficient expression of recombinant fibrinogen and variants thereof in intact form in a eukaryotic cell culture system.

Abstract: Provided are degradation-resistant fibrinogen sealants comprising a first composition comprising one or more of fibrinogen ?A/?? heterodimers and/or fibrinogen ??/?? homodimers and a second composition comprising thrombin and, optionally, degradation-resistant fibrinogen sealants disclosed herein may further comprise Factor XIII and calcium. Degradation-resistant fibrinogen sealants are suitable for the treatment of trauma, particularly vascular trauma.

Abstract: The invention is directed to biomarkers for determining the EGFR kinase activity in a subject, and the use thereof for predicting and monitoring therapeutic intervention in cancer patients. Areas of application are the life sciences: biology, biochemistry, biotechnology, medicine and medical technology. The biomarkers are selected from a first group consisting of Amy 1, Apo Al, Carbx, Casp, AFP, ApoM, SAP, Fib-a, Fib-b, Fib-g, ApoE, A2MG, A2MG isoform, Serpin, Clusterin, MHC-fB, SAP isoform, or from a second group consisting of Gpx3, properidin, MUP1, HMW-K, Lifr-p, Orm 1, MBL-A, MBP-C, wherein the biomarkers are regulated by EGF overexpression in a subject.

Abstract: A novel protein and a fragment thereof useful as a tumor marker of pancreatic cancer are disclosed. This protein or a fragment thereof is a modified ?-fibrinogen protein containing an oxidized amino acid residue(s) or a fragment thereof containing said oxidized amino acid residue(s). The oxidized amino acid residue(s) is one or more amino acid residues selected from the group consisting of (a) a proline residue corresponding to the proline residue at the position of 530 in SEQ ID NO: 2, and (b) a proline residue corresponding to the proline residue at the position of 565 in SEQ ID NO: 2.

Abstract: A method of treating a disorder characterized by tissue damage is provided. The method comprising providing to a subject in need-thereof a composition which comprises a synthetic polymer attached to denatured fibrinogen or a therapeutic portion of the fibrinogen, the composition being formulated for releasing the therapeutic portion of the fibrinogen in a pharmacokinetically regulated manner, thereby treating the disorder characterized by tissue damage or malformation.

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

Abstract: Provided is a pulverized fibrin clot and a pharmaceutical composition including a pulverized fibrin clot. The pharmaceutical composition may contain the pulverized fibrin clot suspended in a gel such as cross-linked hyaluronic acid. The pharmaceutical composition may be in a form suitable for injection and may be used, for example, in the treatment of connective tissue, such as skin connective tissue. Also provided is a method for preparing a pulverized fibrin clot as well as a method for treating connective tissue using the pharmaceutical composition.

Abstract: It is an object of the present invention to provide a method for chemically modifying biopolymer and polypeptide with a hydrophobic compound or a compound which causes degradation or reaction under basic condition. The present invention provides a method for producing a chemically modified biopolymer or polypeptide, wherein a biopolymer or polypeptide is chemically modified in a reaction solution containing an organic fluorine compound.

Abstract: The invention is directed to formation and use of electroprocessed fibrin as an extracellular matrix and, together with cells, its use in forming engineered tissue. The engineered tissue can include the synthetic manufacture of specific organs or tissues which may be implanted into a recipient. The electroprocessed fibrin may also be combined with other molecules in order to deliver the molecules to the site of application or implantation of the electroprocessed fibrin. The fibrin or fibrin/cell suspension is electrodeposited onto a substrite to form the tissues and organs.

Abstract: The invention provides compositions and methods for harvesting and enriching cells such as connective tissue progenitors cells using stirred bioreactors, and in some embodiments fibrin microcarriers.

Abstract: The present invention relates to sealants for skin and other tissues. The sealants include an electroprocessed material. The sealants may contain more than one electroprocessed materials and may contain additional substances. The invention further relates to methods of making and using such sealants.

Abstract: The present invention relates to processes for the purification of fibrinogen, and to readily solubilised fibrinogen preparations.

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: A process for isolation and purification of a target protein by chromatography wherein the chromatography removes or depletes prions (PrPSC), comprising the steps of contacting a potentially PrPSC contaminated sample comprising a target protein with a multimodal chromatographic material; setting buffer conditions so that the target protein is bound to the multimodal chromatographic material and whereas PrPSC is not binding to the multimodal chromatographic material; followed by elution of the target protein. a process for isolation and purification of a target protein free of prion protein (prpSC).