Abstract: Disclosed is a fusion protein including an Ixodes ricinus salivary gland polypeptide. In particular, it relates to a fusion protein including at least one Ixodes ricinus salivary gland polypeptide, at least one serum albumin polypeptide and at least one linker peptide. Also disclosed is the use of such a fusion protein for preventing or treating thrombus formation and/or thrombus growth, as well as pharmaceutical compositions, medicaments and methods including such a fusion protein.

Abstract: The present invention provides methods for identifying genes and pathways involved in plasticity. The invention applies some of these methods to identify genes that are differentially regulated in at least a portion of the nervous system of an individual subjected to conditions known to result in altered nervous system plasticity, i.e., dark rearing (DR) or monocular deprivation (MD). The genes are targets for pharmacological agents that modify plasticity. The invention also identifies biological pathways that are enriched in genes that are differentially regulated under conditions known to result in altered nervous system plasticity. The present invention further provides methods and compositions for modifying plasticity in the nervous system of a subject.

Abstract: The invention relates to a humanized form of an antibody capable of preventing tissue factor (coagulation factor F3) signaling but which does not interfere with Factor VII binding or FX binding to tissue factor and does not prolong coagulation time. The antibody of the invention is useful in treating conditions, such as tumor progression, in which the associated cells express tissue factor and tissue factor signaling occurs.

Abstract: The invention provides methods of making and using compounds of the formula shown, which are inhibitors of human plasmin and plasma kallikrein. (Formula I) The compounds are useful for the prevention of blood loss, and as components of fibrin adhesives.

Abstract: The invention relates to a new polynucleotide which encodes a polypeptide expressed in the salivary glands of ticks, more particularly the Ixodes ricinus arthropod tick, during the slow-feeding phase of the blood meal have, said polynucleotide and related polypeptide may be used in different constructions and for different applications which are also included in the present invention.

Abstract: A streamlined method for purifying alpha-1-antitrypsin (AAT) from an AAT-containing protein mixture, such as a Cohn fraction IV precipitate, is provided. In the method of the invention, contaminating proteins are destabilized by cleavage of disulfide bonds with a reducing reagent, such as a dithiol, which does not affect AAT. The destabilized proteins are then preferentially adsorbed on a solid protein-adsorbing material, without the addition of a salt as a precipitant. Separation of the solid adsorbent from the solution leaves a purified AAT solution that is directly suitable for chromatographic purification, without the need for extensive desalting as in prior art processes. A process incorporating this method, which provides pharmaceutical grade AAT in high yield on a commercial scale, is also described.

Abstract: Compositions and methods are disclosed that relate to novel plasmin-inhibiting polypeptides that are structural variants of a human TFPI-2 Kunitz-type proteinase first inhibitor domain (KD1). The polypeptides are potent plasmin inhibitors and in certain embodiments have anti-fibrinolytic activity and/or decreased anti-coagulation activity relative to wild-type TFPI-2 KD1 and are not highly immunogenic. The plasmin-inhibiting polypeptides will find uses as anti-cancer agents, as antifibrinolytic agents, as protease inhibitors, and in other contexts.

Abstract: Conjugates of hydroxyalkyl starch and a protein are provided herein. The conjugates are formed by a covalent linkage between the hydroxyalkyl starch or a derivative of the hydroxyalkyl starch and the protein. Methods of producing the conjugates and the use of the conjugates also are provided herein.

Abstract: Modified Factor IX (FIX) polypeptides and uses thereof are provided. Such modified FIX polypeptides include FIXa and other forms of FIX. Among the modified FIX polypeptides provided are those that have altered activities, typically altered procoagulant activity, including increased procoagulant activities. Hence, such modified polypeptides are therapeutics.

Abstract: Methods for inhibiting activated protein C (APC) comprising contacting the APC with a Kunitz polypeptide in an amount effective in inhibiting the activity of APC, wherein the Kunitz polypeptide comprises six cysteine residues at positions corresponding to positions 7, 16, 32, 40, 53, and 57 in SEQ ID NO:1, a motif X1GX2CBX? at positions corresponding to positions 13-18 in SEQ ID NO:1, wherein each of X1 and X2, independently, is any amino acid residue, B is a basic amino acid residue, and X? is G, A, or V; and at least one heparin-binding motif, which can present at the C-terminus of the Kunitz polypeptide.

Abstract: The invention provides compounds that are effective as inhibitors of human plasmin and plasma kallikrein, and that are useful for the prevention of blood loss and as components of fibrin adhesives. The invention further provides methods of making and using the compounds.

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: Techniques, methods and lavages are disclosed for prevention or treatment of shock, particularly cecal ligation or cecal inoculation shock, by administering a specific therapeutic agent, which is able to use smaller volumes of reagent to achieve partial to complete inhibition, than other previously described techniques. The agent includes a combination of enzyme inhibitor, cytotoxic lipid binding protein, and antibiotic.

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: The invention relates to a new polynucleotide which encodes a polypeptide expressed in the salivary glands of ticks, more particularly the Ixodes ricinus arthropod tick, during the slow-feeding phase of the blood meal have, said polynucleotide and related polypeptide may be used in different constructions and for different applications which are also included in the present invention.

Abstract: The invention relates to Fmoc (9-fluorenyl-methoxycarbonyl)-based polymeric conjugates. These conjugates are useful for extending the in-vivo circulation of protein and peptide drugs.

Abstract: The invention relates to a new polynucleotide which encodes a polypeptide expressed in the salivary glands of ticks, more particularly the Ixodes ricinus arthropod tick, during the slow-feeding phase of the blood meal have, said polynucleotide and related polypeptide may be used in different constructions and for different applications which are also included in the present invention.

Abstract: The present invention provides methods for treating interstitial lung diseases, comprising administering to an individual an effective amount of an inhibitor of coagulation factor XII. The invention further provides uses and pharmaceutical kits for that treatment.

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: 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 invention relates to the therapeutic application of the Kazal-type serine protease inhibitor Infestin or domains thereof or modified Kazal-type serine protease inhibitors based on Infestin homologs, which prevent the formation and/or stabilization of three-dimensional arterial or venous thrombi by interfering with proteins involved in activation of the so-called intrinsic coagulation pathway. The present invention also relates to the use of Kazal-type serine protease inhibitors or fragments thereof or modified Kazal-type serine protease inhibitors in the treatment or prophylaxis of a condition or disorder related to arterial thrombus formation, i.e. stroke or myocardial infarction, inflammation, complement activation, fibrinolysis, angiogenesis and/or diseases linked to pathological kinin formation such as hypotonic shock, edema including hereditary angioedema, bacterial infections, arthritis, pancreatitis, or articular gout, Disseminated Intravasal Coagulation (DIC) and sepsis.

Abstract: The present invention relates to the use of at least one antibody and/or one inhibitor for inhibiting factor XII and preventing the formation and/or the stabilization of three dimensional thrombi. It also relates to a pharmaceutical formulation and the use of factor XII as an anti-thrombotic target.

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.

Abstract: Methods are described for preventing or reducing ischemia, e.g., cerebral ischemia, and/or reperfusion injury, e.g., reperfusion injury associated with cerebral ischemia, in a patient.

Abstract: A polymeric prodrug composition including a hydrogel, a biologically active moiety and a reversible prodrug linker. The prodrug linker covalently links the hydrogel and the biologically active moiety at a position and the hydrogel has a plurality of pores with openings on its surface. The diameter of the pores is larger than that of the biologically active moiety at least at all points of the pore between at least one of the openings and the position of the biologically active moiety.

Abstract: Provided is a vector for use in delivering a therapy to or removing a therapy from a site within a patient, wherein the vector comprises: a) a binding moiety; and b) a therapeutic agent, wherein the binding moiety comprises a metal-binding protein, polypeptide or peptide which is bound to or encapsulates a magnetic or magnetisable substance, and wherein the vector is to be administered using a device comprising an electromagnet and an element suitable for bringing the therapeutic agent into proximity with the site.

Abstract: The present invention relates to a method for lowering the viscosity of compositions comprising Vitamin K-dependent proteins.

Abstract: The present invention is directed to a hemostatic composite structure having a bioabsorbable fabric or non-woven substrate having at least two major oppositely facing surface areas and a continuous non-porous polymer-based film that is laminated on one major surface of said substrate. The bioabsorbable fabric substrate can be an oxidized polysaccharide and/or the non-woven substrate can be made from bioabsorbable, non-cellulosic derived polymers. The continuous non-porous polymer based film can be a bioabsorbable polymer. The present invention also relates to a method for providing hemostasis by applying a composite structure described herein onto a wound site in need of a hemostatic device wherein a major surface of the substrate without the film layer is applied onto the wound site.

Abstract: The invention provides a method for preventing formation of inhibitors to blood coagulation factor VIII or factor IX in a subject having haemophilia, the method comprising administering (via intravenous, subcutaneous, intradermal, or intramuscular routes) to a previously untreated subject an effective dosage of factor VIIa or a factor VII-related polypeptide.

Abstract: The present invention relates to a polypeptide exhibiting a protease inhibitory activity and uses of said polypeptide in methods for inhibiting, directly or indirectly, one or more proteases of the blood clotting cascade. The invention also relates to use of said polypeptide as a pharmaceutical e.g. for prophylactic or ameliorating treatment of blood clots. In addition the invention comprises methods for production of said polypeptide.

Abstract: Novel biodegradable compositions are disclosed. The biodegradable compositions include at least one hydroxyl-terminated component and at least one bioactive peptide in a linear chain. The compositions may be utilized as medical devices including drug delivery devices, tissue adhesives and/or sealants.