Abstract: The present invention relates to novel analogues of neuropeptide Y, pharmaceutical compositions containing the same, pharmaceutical formulations containing the same, and method of treating diseases or conditions mediated by neuropeptide Y-receptor binding. More particularly, the present invention relates to novel analogues of neuropeptide Y having proline substitution at position 34 and other substitution(s) as defined herein that selectively bind to the neuropeptide Y1 receptor subtype compared to the neuropeptide Y2 receptor subtype.

Abstract: An affinity substrate for selectively binding a coagulation protein, includes a substrate solid on which nucleic aptamers binding specifically to the coagulation protein are immobilized.

Abstract: The use for the manufacture of a medicament for preventing unwanted coagulation during surgery, and particularly a Coronary Artery By pass Graft (CABG) procedure, of boronic acids of formula (I), and salts, prodrugs and prodrug salts thereof; wherein Y comprises a moiety which, together with the fragment —CH(R9)—B(OH)2, has affinity for the substrate binding site of thrombin; and R9 is a straight chain alkyl group interrupted by one or more ether linkages and in which the total number of oxygen and carbon atoms is (3, 4, 5) or (6) or R9 is —(CH2)m—W where m is (2, 3, 4) or (5) and W is —OH or halogen (F, CI, Br or I).

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

Abstract: Medical devices having a catalyst capable of catalyzing the generation of nitric oxide in vivo and methods of treating a vascular condition using the devices are provided.

Abstract: This invention relates to methods of expressing eukaryotic proteins in prokaryotic hosts, particularly eukaryotic proteins that require formation of disulfide bridges for biological activity. Various approaches are used including fusion to thioredoxin, cytoplasmic expression of disulfide isomerases, deficiencies in thioredoxin and/or glutathione reductases, deficiencies in proteases, and the like. The method is applicable to express monomeric and dimeric forms of the eukaryotic protein with biological activity such as monomeric and dimeric forms of a disintegrin or a disintegrin domain. Included are the vectors, host cells expressing the proteins, the expressed proteins and methods of using the proteins.

Abstract: The invention relates to procedures and methods of determining a susceptibility to cardiac arrhythmia, including Atrial Fibrillation, Atrial Flutter and Stroke, by assessing the presence or absence of alleles at polymorphic markers found to be associated with risk of these conditions. The invention further relates to kits encompassing reagents for assessing such markers, and diagnostic 5 methods, uses and procedures for utilizing such susceptibility markers.

Abstract: A biodegradable cross-linked cationic multi-block copolymer of linear polyethylenimine (LPEI) wherein the LPEI blocks are linked together by hydrophilic linkers with a biodegradable disulfide bond and methods of making thereof. The biodegradable cross-linked cationic multi-block copolymer may also contain pendant functional moieties which are preferably receptor ligands, membrane permeating agents, endosomolytic agents, nuclear localization sequences, pH sensitive endosomolytic peptides, chromogenic or fluorescent dyes.

Abstract: The present inventors succeeded in constructing bispecific antibodies, which bind to both the blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X, and functionally substitute for blood coagulation factor VIII/activated blood coagulation factor VIII which enhances the enzymatic reaction.

Abstract: A method for preventing stroke in a patient suffering from atrial fibrillation, wherein the patient has at least one risk factor for major bleeding events, the method comprising administering to the patient 110 mg b.i.d. of dabigatran etexilate, optionally in the form of a pharmaceutically acceptable salt thereof.

Abstract: The invention provides low-half life fibrinogen as a result of recombinant expression or enzymatic and chemical removal. The low-half life fibrinogen is useful in treating or effecting prophylaxis of bleeding particularly in situations of an acute nature in which a high initial dose and rapid decline to normal or below normal levels is desirable.

Abstract: A method of inactivation of infectious agents in a fluid containing plasma protein and potentially containing at least one infection agent which includes unique steps of placing the fluid in a container which is resistant to leakage under high pressure, placing the container in a compression chamber, pressurizing the fluid inside the container to a pressure sufficient to inactivate the potential infectious agent, pressurizing the fluid under a high pressure for a time duration sufficient to inactivate the potential infectious agent and pressurizing the fluid under the high pressure at an initial temperature that does not inactivate coagulation factors under the conditions. The present invention also includes a fluid containing plasma proteins which is pressurized to inactivate infectious agents, the plasma proteins containing serum albumen and at least one coagulation factor.

Abstract: The invention provides a pharmaceutical composition comprising at least one polypeptide of the following (a) to (d): (a) a polypeptide comprising the amino acid sequence of SEQ ID NO:1; (b) a polypeptide comprising an amino acid sequence comprising one or more amino acid deletions, insertions, substitutions or additions in the amino acid sequence of the above (a) and having a platelet aggregation inhibitory activity and/or a platelet adhesion inhibitory activity; (c) a polypeptide comprising the amino acid sequence of SEQ ID NO:3; and (d) a polypeptide comprising an amino acid sequence comprising one or more amino acid deletions, insertions, substitutions or additions in the amino acid sequence of the above (c) and having a platelet aggregation inhibitory activity and/or a platelet adhesion inhibitory activity, as an active component.

Abstract: The invention relates to substances which inhibit the binding of oxidized proteins to CD36 or inhibit the functions of CD36 that are induced by the interaction of CD36 with oxidized proteins. The invention also relates to the use of these substances as medicaments for humans and animals. In one embodiment, a medicament includes an oxidized protein, an oxidized peptide, or structural analog or mimetic thereof. Methods for prophylaxis or therapy of acute infections, inhibition of angiogenesis, and improvement of hemostasis include administering to an animal or human in need thereof an effective amount of a medicament including an oxidized protein, an oxidized peptide, or structural analog or mimetic thereof. An example of an acute infection is Human Immunodeficiency Virus (HIV).

Abstract: A hydrogel system comprising polymer-conjugated albumin molecules is provided for controlled release delivery of therapeutic agents. The polymer is a functionalized synthetic polymer, preferably PEG-diacrylate. The polymer-conjugated albumin is preferably mono-PEGylated albumin. The hydrogel system may comprise a matrix to which the polymer-conjugated albumin molecules are linked via a functional group of the polymer. The matrix may be formed from the same polymer of the polymer-albumin conjugate.

Abstract: Methods for treating bleeding disorders using non-anticoagulant sulfated polysaccharides (NASPs) as procoagulants are disclosed. NASPs can be administered as single agents, or in combination with one another, or with other medications (such as factors VII, VIII and IX) to promote hemostasis. In particular, the use of NASPs in treatment of bleeding disorders, including congenital coagulation disorders, acquired coagulation disorders, and trauma induced hemorrhagic conditions is described.

Abstract: A method of modulating transplant organ size in a subject in need thereof is disclosed. The method comprising: (a) administering to the subject an agent capable of modulating an activity or expression of a coagulation factor or an effector thereof; and (b) transplanting the organ into the subject; thereby modulating the transplant organ size in the subject.

Abstract: The present invention relates to recombinant blood coagulation factor IX (rFIX) mutants having factor VIII (FVIII) independent factor X (FX) activation potential. Five full length FIX proteins with combinations of mutations of amino acids important for functional activity of FIX and FIX wild type were cloned and expressed in HEK 293 cells. The proteins were tested by an activated partial thromboplastin time (aPTT) assay in FVIII-depleted plasma as well as in FVIII-inhibited patient plasma. In FVIII-depleted plasma functional activity of the FIX mutants was calculated as increased FVIII equivalent activity. The mutant proteins had increased FVIII equivalent activity. In FVIII-inhibited patient plasma the FEIBA equivalent activity was calculated for analysis of FVIII independent FX activation potential. The proteins had also increased FEIBA equivalent activity. Furthermore, the pre-activated FIX proteins had an increased activity in FIX-depleted plasma containing FVIII inhibitors.

Abstract: The invention relates to conjugated proteins, in particular but not exclusively, blood coagulation factors, to processes for preparing said conjugates, to pharmaceutical compositions comprising said conjugates and to the use of the conjugates in therapy, in particular but not exclusively, for the treatment of diseases alleviated by blood coagulation factors such as the prophylactic treatment of hemophilia.

Abstract: A 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: Disclosed herein are recombinant proteins capable of inducing platelet aggregation and uses thereof.

Abstract: Provided is an encapsulated functional fine particle composition capable of spraying that is useful for hemostasis and wound protection and allows a patient to treat the wound by oneself. Additionally, the composition can be rapidly applied on a large wound during an operation using an air gun in case of in-vivo application and shows prompt hemostasis.

Abstract: Described are methods of modulating stem/progenitor cell recruitment involving molecules that agonize the formation of plasmin stimulating the recruitment of stem/progenitor cells, including hematopoietic and endothelial precursor cells. Conversely, antagonists of plasmin can inhibit recruitment of the stem cells. In addition, the identification of the uPA receptor (uPAR) as a retention signal for stem cells in their niche suggests a novel method for increased engraftment and isolation of multipotent stem cells.

Abstract: The present invention relates to the discovery of the Aegyptin gene and Aegyptin protein, a molecule that interacts with collagen and inhibits platelet adhesion, activation and aggregation. Novel biological tools, prophylactics, therapeutics, diagnostics, and methods of use of the foregoing are also disclosed.

Abstract: Methods of treating hemorheologic abnormalities in mammals are provided, as well as methods of evaluating circulatory flow mechanics by analyzing hemorheologic determinants or hemorheologic abnormalities in the blood.

Abstract: The present invention provides conjugates having a releasable linkage. Methods of making conjugates, and methods for administering conjugates, are also provided.

Abstract: The present invention relates to conjugates of Factor IX that have been modified to include a biocompatible polymer moiety. The Factor IX conjugates are substantially free of contamination by Factor IXa. The Factor IX conjugates have improved pharmacokinetic properties, such as increased half-life, which results in dose sparing and less frequent administration.

Abstract: The present invention relates to modified nucleic acid sequences coding for coagulation factor VIII (FVIII) and for von Willebrand factor (VWF) as well as complexes thereof and their derivatives, recombinant expression vectors containing such nucleic acid sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives coded for by said nucleic acid sequences which recombinant polypeptides and derivatives do have biological activities together with prolonged in vivo half-life and/or improved in vivo recovery compared to the unmodified wild-type protein. The invention also relates to corresponding FVIII sequences that result in improved expression yield. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such modified nucleic acid sequences.

Abstract: A method for preventing the formation of a bivalirudin precipitate during preparation of a pharmaceutical drug product comprising about 250 mg of bivalirudin, a dried bivalirudin drug product, and a concentrated liquid bivalirudin drug product. The method for preventing the formation of a bivalirudin precipitate comprises (i) preparing an aqueous solution comprising a buffer and a pH greater than the isoelectric point of bivalirudin; (ii) adding bivalirudin salt to the aqueous solution to form a bulk solution; (iii) transferring the bulk solution to one or more vessels; and (iv) drying the bulk solution. The buffer may have a pKa of about 4 to less than 7, and a pH greater than the isoelectric point of bivalirudin. The pH of the bulk solution may be maintained at a level greater than the isoelectric point of bivalirudin. Further, the bulk solution may have a final pH of about 4 to about 7.

Abstract: Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.

Abstract: Disclosed are compositions and methods related to clot-binding compounds. For example, disclosed are compositions comprising a surface molecule and at least one modified clot-binding compound. The modified clot-binding compound can selectively bind to clotted plasma protein, wherein the composition causes clotting and amplifies the accumulation of the composition in tumors. The modified clot-binding compound can enhance the clotting in tumors compared to its unmodified derivative. The disclosed targeting is useful for treatment of cancer and other diseases and disorders.

Abstract: A medical implant device having a substrate with an oxidized surface and a silane derivative coating covalently bonded to the oxidized surface. A bioactive agent is covalently bonded to the silane derivative coating. An implantable stent device including a stent core having an oxidized surface with a layer of silane derivative covalently bonded thereto. A spacer layer comprising polyethylene glycol (PEG) is covalently bonded to the layer of silane derivative and a protein is covalently bonded to the PEG. A method of making a medical implant device including providing a substrate having a surface, oxidizing the surface and reacting with derivitized silane to form a silane coating covalently bonded to the surface. A bioactive agent is then covalently bonded to the silane coating. In particular instances, an additional coating of bio-absorbable polymer and/or pharmaceutical agent is deposited over the bioactive agent.

Abstract: Disclosed is a method for preventing or treating thrombosis in a mammal such as a primate and particularly a human patient. A preferred method includes administering to the mammal a therapeutically effective amount of at least one humanized antibody, chimeric antibody, or fragment thereof that binds specifically to human tissue factor (TF). Additional methods and kits are provided.

Abstract: The present invention relates to a method for identifying responders to a blockade of integrin receptors, as well as to a method for determining responsiveness to a treatment involving with said blockade in a patient in need of such treatment. Furthermore, the present invention relates to a kit for use in said methods.

Abstract: The invention relates to the field of radiation injury. More particularly, this invention relates to the protection against/prevention of and treatment of diseases caused by ionizing radiation by the use of thrombomodulin.

Abstract: The present invention provides methods, compositions, and kits wherein nanomaterials are used for inhibiting cancer stem cell division, colony formation, spheroid formation and self-renewal. The present invention also provides methods, compositions, and kits wherein nanomaterials are used for treating cancer, coating tumors, and inhibiting metastasis. The present invention also provides methods, compositions, and kits wherein nanomaterials are used for inducing cells to go into stasis. The present invention further provides methods for isolating tumors, inhibiting bleeding, and marking margins of tumors and organs during surgery with a nanomaterial.

Abstract: The described invention provides a nonhuman animal model system for hemorrhagic brain conditions, methods for evaluating a substance for treating the hemorrhagic brain condition in a mammal, methods for treating hematoma expansion or recurrent rebleeding resulting from hemorrhagic brain conditions in a mammal, and pharmaceutical compositions for administration into or at a distance proximal to the hemorrhagic brain condition.

Abstract: The present invention relates generally to methods and compositions for targeting and delivering solid-phase platelet-dependent vascular occlusion agents. In particular, particles or coils or stents coated with platelet binding agents are directed to target vasculature, such as the vasculature of solid tumor masses or AV-malformations or aneurysms or endoleaks; the solid-phase agent then binds and activates platelets, which in turn bind and activate other platelets. This process results in the rapid formation of a platelet-mediated thrombus about the solid-phase agent causing vessel occlusion.

Abstract: Provided are lipidic particles comprising phosphatidylcholine, phosphatidylinositol and cholesterol. Also provided are compositions comprising the lipidic particles and having associated therewith therapeutic agents such as peptides, polypeptides or proteins. In these compositions, the therapeutic agents have reduced immunogenicity and/or longer circulating time. These compositions can be used for therapeutic administration of the peptides, polypeptides and/or proteins.

Abstract: A composition for transdermal delivery, particularly iontophoretic transdermal delivery, having at least one cationic active agent or a salt thereof. The composition comprises at least one cationic active agent or a salt thereof, at least one polyamine and/or polyamine salt, water or an aqueous solvent mixture, and optionally one or more additives. Use of the composition as a component of a transdermal patch or of an iontophoretic transdermal patch is also provided, as well as the use of the composition in a method for transdermally or iontophoretically administering cationic active agents. A method for determining the in vitro skin permeation properties of an active agent-containing iontophoretic composition is also provided.

Abstract: The present invention relates to a von Willebrand Factor for use in the treatment and/or prevention of a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes. Furthermore, the present invention relates to a method of treating and/or preventing a disorder related to a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes comprising administering a pharmaceutically effective amount of a von-Willebrand-Factor (vWF) to a patient in need thereof. The present invention also relates to a composition comprising vWF and a composition comprising FVIII for simultaneous, separate or sequential use for use in the treatment and/or prevention of a bleeding event associated with a thrombopathy induced by substances inhibiting thrombocytes.

Abstract: A method of factor XI-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject. A method of factor XI-dependent blood coagulation enhancement in a subject in need of enhanced blood coagulation comprising: (i) selecting a subject that is not deficient for factor XI; and (ii) administering a therapeutically effective amount of a composition comprising a non-anticoagulant sulfated polysaccharide (NASP) to the subject, wherein the NASP enhances blood coagulation in a factor XI-dependent manner.

Abstract: The present invention relates to inhibition of heparinoids anti-coagulation activity by a non-active form of a eukaryotic endoglycosidase or any fragment or peptide thereof comprising at least one heparin-binding domain. More particularly, the invention provides compositions and methods for the inhibition of heparinoids anti-coagulation activity and for the treatment of coagulation related pathologic clinical conditions, using a non-active form of mammalian heparanase or peptides thereof comprising at least one heparin-binding domain.

Abstract: The instant invention provides methods and compositions for the treatment, prevention and diagnosis of for example, platelet aggregation or clot formation in a subject. The invention inhibits the activity of decreases the amount of neutrophils in the subject by inhibiting the activity or production of IL-6, interferon-gamma, STAT1, or cathepsin D. The invention addresses decreasing the amount of neutrophils in an attempt to treat subjects that have or are at risk of developing a vascular occlusive disease, an ischemia or reperfusion injury, an acute or chronic inflammatory state, autoimmune disease, myelodysplastic syndrome, tissue injury from surgery or accidental trauma, acute bacterial or viral infection, has undergone a microvascular surgical reconstructive procedure, is receiving granulocyte colony stimulating factor therapy, receiving stem cell therapy, or has sickle cell anemia.

Abstract: Methods, compositions and kits are disclosed for identifying patients with an increased risk of experiencing an adverse cardiovascular event where the patient is undergoing aspirin antiplatelet therapy. A platelet-containing sample from the patient is evaluated for platelet hyperactivity and platelet hyperactivity in the sample is related to the patient's risk of an adverse cardiovascular event. In some embodiments the evaluation for platelet hyperactivity is carried out by assessing the function of platelets in the sample using a high shear platelet function test.

Abstract: The present invention relates to methods and tools for producing large quantities of gamma-carboxylated protein comprising: (i) culturing a cell adapted to express a protein which requires gamma-carboxylation and ?-glutamyl carboxylase in a ratio of at least 10:1, under conditions suitable for expression of both proteins, and (ii) isolating gamma-carboxylated protein.

Abstract: In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a living subject. In one embodiment, the invention provides methods of treating a subject suffering from a complement mediated coagulation disorder, such as disseminated intravascular coagulation. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In some embodiments, the MASP-2 inhibitory agent inhibits cellular injury associated with MASP-2-mediated alternative complement pathway activation, while leaving the classical (C1q-dependent) pathway component of the immune system intact. In another aspect, the invention provides compositions for inhibiting the effects of lectin-dependent complement activation, comprising a therapeutically effective amount of a MASP-2 inhibitory agent and a pharmaceutically acceptable carrier.

Abstract: A haemostatic kit to be used as a medical device provides for a containment unit and a haemostatic agent in said containment unit, said haemostatic agent occupying less than 90% of the volume of the containment unit. This allows for facile and consequently sterile preparation of, for instance, a gelatin paste for use in haemostatis when combined with saline, thrombin or another agent to assist in haemostatis.

Abstract: Disclosed are compositions and methods related to clot-binding head groups. The disclosed targeting is useful for treatment of cancer and other diseases and disorders.

Abstract: Targeted coagulation factors comprising a coagulation factor linked with at least one domain that specifically binds to a membrane protein on a blood cell is provided. The disclosed targeted coagulation factors increase the efficiency of coagulation factors and prolong their duration of action and thus, are an improvement for the treatment of hematological diseases such as hemophilia A.