Abstract: The invention relates to an immunoglobulin composition reduced in thrombogenic agents and to methods for its preparation. One method comprises subjecting an immunoglobulin containing solution to a negative cation exchanger chromatography at a pH in the range of higher than 3.8 to equal to or lower than 5.3. The solution can also be subjected to a negative anion exchanger chromatography at a pH in the range of 7 to 8.2.

Abstract: The invention comprises the use of LGF in the production of medicinal products that can be used in the pleiotropic tissue regeneration of one or more damaged tissues, in which at least one of the damaged tissues forms part of the central nervous system and the medicinal product is intended to be administered systemically. The invention is based on the fact that intraperitoneal administration of LGF can promote a positive effect on a Parkinson's disease model. As such, in a preferred embodiment of the invention, the medicinal product is intended for the treatment of Parkinson's disease, particularly when the medicinal product is intended for humans.

Abstract: Disclosed are methods for producing implantable bone compositions suitable for attaching stem cells thereto, characterized in that bone particles are contacted with an albumin comprising solution. Said bone particles can be mineralized and/or lyophilized bone particles of animal or human origin. Preferably the non-immunogenic albumin comprising solution is lyophilized onto said bone particles. The invention further concerns bone compositions suitable for use in graft implantation obtainable by said methods.

Abstract: The present invention relates to compounds, compositions, methods and/or kits for determining and/or predicting and/or diagnosing and/or treating restenosis in a patient.

Abstract: The present invention relates to methods for the diagnosis of impaired cardiac function/heart disease. The present invention provides a method of diagnosing heart disease in a subject, said method comprising determining the level of CgB or SgII, or fragments thereof, in a body fluid of said subject. Such methods can also be used to determine the clinical severity or prognosis of heart disease in a subject.

Abstract: Provided is a novel, isolated polypeptide including an amino acid sequence of SEQ. ID. NO: 2 or SEQ. ID. NO: 4, and the nucleic acid molecule which encodes it. The polypeptide may be used in a method for treating various diseases including cancer, immune associated, viral and inflammatory diseases.

Abstract: The present invention concern a composition or a patch adapted for the prophylactic or therapeutic treatment by continuous subcutaneous administration of a subject suffering from atherosclerosis, comprising an effective amount of at least one epitope derived from a protein present in the atherosclerotic plaque, whereby administration of said at least one epitope to said subject induces a specific regulatory immune response, preferably a Treg response.

Abstract: A composition comprising Human Serum Albumin and an Amino Acid Solution, a method of making the same, and a method for use, including treating acute hypovolemia due to any number of medical conditions due to sepsis with shock, hemorrhagic shock, hypovolemic shock, burn injury, capillary leak syndrome, hypoalbuminemia, nephritic syndrome, or multi-organ failure with third space fluid loss from any other medical disease.

Abstract: The present invention related to the use of Cystatin in predicting onset of migraines. The invention also relates to the use of Cystatin as a vasodilatory agent. The invention also relates to antagonists to Cystatin for use in treating and preventing and treating migraine attacks.

Abstract: The goal of the present invention is to provide substances to prevent diseases by activating inherently possessed functions, for cultured fishes and shellfishes and livestock with tendency of decreased immune function due to densely populated breeding environment, and for humans with tendency of easily lowered immune functions due to complicated social structures and aging. The present invention expresses marked effect in preventing infection and cancer by administrating appropriate dose of swine plasma, swine plasma albumin, peptides isolated from swine plasma and swine plasma albumin, and swine plasma mixture, among others including fine powder of Crustacea (including crust of Crustacea), to activate immune function of Crustacea, Pisces, Aves, Mammals, and humans.

Abstract: The present invention relates to the purification and production of human albumin from various sources through crystallization and repeated crystallization. Basic features of the invented process include providing specific reaction conditions and precipitating reagents to maximize albumin crystallization. Solubility diagrams are utilized as the basis for process control of the invented method. The current invention specifically controls phosphate concentration, pH and temperature to precisely guide crystallization kinetics and crystal yield.

Abstract: A composition useful for separating lipoproteins, such as high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and modified lipoproteins with a high degree of accuracy by ion-exchange based procedures. The composition comprises an organic particle having a hydrophilic surface onto which ion-exchange groups are introduced and which is formulated so as to provide a high enough degree of hydrophilicity to prevent irreversible absorption of lipoproteins, but which is not so high as to block the pores of the ion exchange particles and prevent adequate retention and separation of lipoproteins. A method for making a composition for separating lipoproteins comprising seed polymerization of organic particles, hydrophilic treatment of the organic particles by introducing 0.

Abstract: Method for preparing a factor VIII solution that is essentially free of viruses and essentially devoid of vWF (von Willebrand factor) and factor VIII-vWF complexes by (a) obtaining a starting factor VIII solution devoid of factor VIII-vWF complexes; and (b) filtering the solution through a hydrophilic virus filter.

Abstract: Lethal Toxin Neutralizing Factor has been isolated in purity from opossum serum by high pressure liquid chromatography (HPLC) fractionation. The amino acid sequence from the N-terminal for the first fifteen amino acids of LTNF-n is: Leu Lys Ala Met Asp Pro Thr Pro Pro Leu Trp Ile Lys Thr Glu. Antibodies to LTNF-n and synthetic peptides consisting of fifteen, ten and five amino acids from the N-terminal of the above sequence, designated as LTNF-15, LTNF-10 and LTNF-5 were produced by immunizing Balb/C mice to produce Anti-LTNF-n, Anti-LTNF-15, Anti-LTNF-10 and Anti-LTNF-5. The anti LTNF-n, anti-LTNF-15, anti-LTNF-10 and anti-LTNF-5 react immunologically with all types of toxins derived from animal, plant and bacteria and can be assayed by immunological in vitro test such as ELISA tests. Anti-LTNFs react roughly proportional to lethal dose of biological toxins under in vitro immunological ELISA test similar to the mouse bioassay test.

Abstract: The present invention comprises a method of protecting organs or tissue susceptible to reperfusion-induced dysfunction after ischemia. The method comprises parenterally administering to a patient a therapeutical composition containing natural alpha-1 acid glycoprotein, natural alpha-1 antitrypsin or a mixture thereof. Alternatively, organ or tissue transplants can be contacted with natural alpha-1 acid glycoprotein, natural alpha-antitrypsin or mixtures by perfusing or flushing them with a solution containing natural alpha-1 acid glycoprotein, natural alpha-1 antitrypsin or mixtures thereof in a concentration of 0.1 to 5 g/l.

Abstract: An albumin preparation that prevents onset of hepatic encephalopathy caused by conventional amino acid preparations and enhances an effect of improving the symptoms is provided. The albumin preparation containing amino acids is characterized in that a content of albumin is 0.01 to 1.0 w/v %, a content of plurality of amino acids containing branched amino acid is 5 to 10 w/v %, a content of the branched amino acids is equal to or more than 30 w/w % on the basis of the content of total amino acids and further, the Fischer ratio (branched amino acid/[phenylalanine+tyrosine] (molar ratio)) is equal to or more than 20.

Abstract: Novel human protein C derivatives are described. These derivatives have increased anti-coagulation activity and resistance to inactivation by serpins, compared to wild-type protein C and retain the biological activity of the wild-type human protein D. These derivatives will require either less frequent administration and/or smaller dosage than wild-type human protein C in the treatment of acute coronary syndromes, vascular occlusive disorders, hyper coagulable states, thrombotic disorders and disease states predisposing to thrombosis.

Abstract: The invention is directed to methods of using Ig compositions to prevent and/or treat humans, livestock and/or domesticated animals suffering from stress induced respiratory disorders. The Ig composition comprises a concentrated amount of one or more immunoglobulins selected from the group consisting of alpha, beta, and gamma globulins. Preferably, the Ig composition comprises other antibodies identified as providing an immune response and/or immune factors such as complement and transfer factors. The Ig composition preferably includes immunoglobulins specific to a variety of antigens. In a preferred method, an equine Ig composition is used to treat exercise induced pulmonary hemorrhage in horses.

Abstract: This invention relates to compositions and processes utilized to modulate the immune system of mammals. More particularly, the present invention relates to the use of low molecular weight substantially immunoglobulin free fractions isolated from mammals to induce a stimulated immune response in mammals.

Abstract: This invention relates to compositions utilized to modulate the immune system of non-mammalian vertebrates. More particularly, the present invention relates to the use of low molecular weight substantially immunoglobulin free fractions isolated from mammals to induce a stimulated immune response in non-mammalian vertebrates.

Abstract: A method to facilitate recovery troponin I and/or troponin T from a sample comprising addition of troponin C to the sample or to a surface from which the troponin I and/or troponin T are recovered.

Abstract: Methods and materials for the treatment of human meningococcemia are provided in which therapeutically effective amounts of BPI protein products are administered.

Abstract: Disclosed are methods for treatment of humans exposed to bacterial endotoxin in circulation by administration of bactericidal/permeability-increasing (BPI) protein products. Serologically and hematologically verifiable alleviation of endotoxin mediated increases in circulating cytokines, fibrinolysis and coagulation factors and changes in lymphocyte counts are observed upon such treatment. Also observed is alleviation of endotoxin mediated decreases in systemic vascular resistance index (SVRI) and concomitant increases in cardiac index (CI).

Abstract: The present invention provides methods of inactivating and removing infectious agents from tissues of use in bioprosthetic devices. The methods include the removal and blockage of binding sites on the tissues for the infectious agents. Also provided are methods for blocking a site on an infectious agent that binds to a site on the tissue.

Abstract: A method for purifying human or other alpha-l proteinase inhibitor (&agr;1-PI) from a solution (which may be derived from the milk of a transgenic animal expressing the &agr;1-PI) which comprises contacting the solution with a cation exchange substrate under conditions sufficient to bind non-tg-&agr;1-PI contaminants to the substrate while not substantially binding tg &agr;1-PI to the substrate. Using the preferred embodiment, the purified tg &agr;1-PI contains as little as 40 pg non-&agr;1-PI-whey protein per mg total protein.

Abstract: The present invention relates generally to a method of separating one or more components from a protein mixture. More particularly, this invention is directed to a method of separating one or more components of blood plasma comprising one or more filtration steps using a cellulose-based filter aid. The present invention is useful in the preparation of therapeutics, in particular plasma-based therapeutics for use in humans.

Abstract: The present invention relates to biologically active peptides which specifically inhibit the Factor IX-dependent pathway of blood coagulation. These peptides are based on a specific motif which represents a sequence of Factor VIII (amino acid 1811-1818) involved in binding to activated Factor IX as well as to the intact Factor IX zymogen. Binding of said peptides to Factor IX or activated derivatives thereof effectively inhibits complex assembly with Factor VIII. These peptides thereby specifically interfere in the Factor IX-dependent pathway of thrombin formation, while leaving other haemostatic pathways unaffected. By virtue of this unique specificity, the peptides of this invention are particularly useful in novel pharmaceutical compositions for the treatment of thrombotic disorders.

Abstract: Methods and materials for the treatment of human meningococcemia are provided in which therapeutically effective amounts of BPI protein products are administered.

Abstract: Disclosed are methods for treatment of humans exposed to bacterial endotoxin in circulation by administration of bactericidal/permeability-increasing (BPI) protein products. Serologically and hematologically verifiable alleviation of endotoxin mediated increases in circulating cytokines, fibrinolysis and coagulation factors and changes in lymphocyte counts are observed upon such treatment. Also observed is alleviation of endotoxin mediated decreases in systemic vascular resistance index (SVRI) and concomitant increases in cardiac index (CI).

Abstract: A peptide derivative represented by the following formula or a salt thereof ##STR1## wherein A represents a hydrogen atom, and B represents a phenyl group substituted with a hydroxyl group;said derivative has an antitumor activity stronger than that of dolastatin 10, and is useful as an anticancer or antitumor agent.

Abstract: Liquid and lyophilized reagents for determining prothrombin time and/or fibrinogen levels in a plasma sample are disclosed. The reagents preferably are based on recombinant rabbit tissue factor. Also disclosed is a purified preparation of recombinant rabbit tissue factor having unique properties, and a novel method for making PT reagents.

Abstract: The methods of the present invention provide a simple means for separating active and inactive Alpha Proteinase Inhibitor (API). The methods further provide means for purifying API at high yield (>70%), and at levels of purity (>90%) and activity (>90%) not heretofore available. Moreover, the methods of the present invention are simple (i.e., two chromatographic steps) and efficient; and are thus especially suitable to large scale purification processes. These methods will contribute substantially to alleviating the unmet demand for API for therapeutic purposes.

Abstract: Plasma EPCR has been isolated, characterized and shown to block cellular protein C activation and APC anticoagulant activity. Plasma EPCR appears to be about 43,000 daltons and circulates at approximately 100 ng/ml (98.4.+-.27.8 ng/ml, n=22). Plasma EPCR bound activated protein C with an affinity similar to that of recombinant soluble EPCR (Kd.sub.app approximately 30 nM), and inhibits both protein C activation on an endothelial cell line and APC anticoagulant activity in a one-stage factor Xa clotting assay. Soluble plasma EPCR appears to attenuate the membrane-bound EPCR augmentation of protein C activation and the anticoagulant function of activated protein C. Soluble EPCR has also been detected in urine. Levels of soluble EPCR can rise in inflammatory disease associated with vascular injury and appear to be correlated with inflammation and disease states associated with abnormal coagulation.

Abstract: The present invention provides methods of producing recombinant fibrinogen in a long-term mammalian cell culture system. Disclosed is a method for the production of recombinant fibrinogen, comprising: growing mammalian cells that express recombinant fibrinogen in a serum-free medium for a time of at least one month at a level of at least 5 .mu.g/ml; and then collecting portions of the conditioned medium at least twice during the culturing time of at least one month, with each portion containing at least 5 .mu.g/ml of recombinant fibrinogen. Also disclosed is a method for the production of recombinant fibrinogen, comprising: growing mammalian cells that express recombinant fibrinogen in a serum-free medium at a level greater than 1 .mu.g/ml; collecting at least a portion of the conditioned medium, and then purifying the fibrinogen from the medium by anion-exchange chromatography or affinity chromatography.

Abstract: Methods and materials for the treatment of human meningococcemia are provided in which therapeutically effective amounts of BPI protein products are administered.

Abstract: Analogs of blood factors which are transiently inactive are useful in treatment of diseases characterized by thrombosis. In addition, modified forms of activated blood factors that generate the active blood factor in serum but have extended half-lives are useful in treating hemophilia conditions. These modified forms of the blood factor may be acylated forms which are slowly deacylated in vivo.

Abstract: Analogs of blood factors which are transiently inactive are useful in treatment of diseases characterized by thrombosis. In addition, modified forms of activated blood factors that generate the active blood factor in serum but have extended half-lives are useful in treating hemophilic conditions. These modified forms of the blood factor may be acylated forms which are slowly deacylated in vivo.

Abstract: Disclosed are methods for treatment of humans exposed to bacterial endotoxin in circulation by administration of bactericidal/permeability-increasing (BPI) protein products. Serologically and hematologically verifiable alleviation of endotoxin mediated increases in circulating cytokines, fibrinolysis and coagulation factors and changes in lymphocyte counts are observed upon such treatment. Also observed is alleviation of endotoxin mediated decreases in systemic vascular resistance index (SVRI) and concomitant increases in cardiac index (CI).

Abstract: The use of C1-inactivator for the production of a pharmaceutical for the prophylaxis and treatment of capillary leak syndrome (generalized extravasation) and circulator shock (refractory hypotension) in severe burns or scalds, in polytrauma, in operations under conditions of extracorporeal circulation, in the use of cytokines, endogenous mediators, and mediator hybrids and growth factors produced by genetic engineering, or capillary leak syndrome and veno-occlusive disease of the liver in therapeutically or prophylactically indicated bone marrow transplantation is described.

Abstract: The invention provides methods for stimulating thrombocytopoiesis in a mammal comprising administering to the mammal an effective amount of modified C-reactive protein ("mCRP") or mutant protein expressing neo-CRP antigenicity. Methods for treating thrombocytopenia, and for promoting megakaryocyte growth and maturation in vitro are also provided. Kits and articles of manufacture are further provided which include mCRP or mutant protein expressing neo-CRP antigenicity.

Abstract: The present invention relates to the preparation and use of liquid formulations of plasma proteins, particularly blood coagulation factors. More specifically, the present invention relates to stable liquid formulations of Factor VIII and Factor IX that can be administered by injection or infusion to provide a constant level of the coagulation factor in the blood.

Abstract: A final drug product comprises a plasma protein selected from the group consisting of coagulation factor VIII and factor IX, in an aqueous solution. The concentration of oxygen in the solution is reduced and/or the solution contains an antioxidant. The solution further contains a carbohydrate in a concentration of at least 350 mg/ml. The protein activity after storage for at least 6 months at a temperature of from 0.degree. C. to 40.degree. C. is from 70% to 130% of its initial value. In a process for preparing the final drug product and a method for improving the long-term stability of coagulation factor VIII or factor IX in an aqueous solution, a carbohydrate is included in the solution in a concentration of at least 350 mg/ml and the solution is stored in its final container under an oxygen-reduced atmosphere or includes an antioxidant.

Abstract: Analogs of blood factors which are transiently inactive are useful in treatment of diseases characterized by thrombosis. In addition, modified forms of activated blood factors that generate the active blood factor in serum but have extended half-lives are useful in treating hemophilic conditions. These modified forms of the blood factor may be acylated forms which are slowly deacylated in vivo.

Abstract: A human Activated Protein C preparation with a high specific activity of 3500 U/mg or more and substantially free from thrombin or other proteases which can convert Protein C into Activated Protein C is provided. A process for preparing this human Activated Protein C, which involves, contacting a solution of human Activated Protein C, after activation of Protein C with thrombin or other activating protease, with a cation exchanger to allow for adsorption of both thrombin or another activating protease and Activated Protein C to the cation exchanger followed by elution of the human Activated Protein C alone.

Abstract: A process for reducing degradation of recombinant coagulation factor VIII caused by metal-dependent proteases requiring Zn.sup.2+ for activity or containing Zn.sup.2+ as an integral part of their structure comprises adding an inhibitor of Zn.sup.2+ dependent proteases to a recombinant factor VIII solution. The recombinant factor VIII solution is obtained after harvesting a conditioned medium from a cell culture used for producing the recombinant coagulation factor VIII. The inhibitor is selected from complexing agents with a stronger affinity for the Zn.sup.2+ ion of the protease than for the ion or ions stabilizing the factor VIII molecule, and compounds structurally related to the natural substrate of the protease and containing an electronegative moiety.

Abstract: The invention is directed to human serum albumin-porphyrin (HSA-P) complexes which are capable of reversible oxygen binding and their uses. These complexes may be used in applications requiring physiological oxygen carriers such as in blood substitute solutions, or in applications requiring plasma expanders. Methods for the production of these complexes are provided. In a specific example, HSA-P complexes are shown to exhibit reversible oxygen binding. In another example, the HSA-P complex does not exhibit appreciable vasoactivity.

Abstract: The invention relates to a pharmaceutical preparation comprising a plasma protein wherein said preparation is free of infectious agents as well as essentially free of denaturation products and is obtainable by a method that encompasses the following steps:a) addition of a polyether and a chaotropic agent to a solution comprising the plasma protein, optional lyophilization of the solution;b) inactivation of infectious agents in the presence of the polyether by a physio-chemical or chemical treatment, andc) removal of the polyether and the chaotropic agent.

Abstract: This invention is related to an adhesive composition which may be used to bond or seal tissue in vivo. The adhesive composition is readily formed from a two component mixture which includes a first part of a protein, preferably a serum albumin protein, in an aqueous buffer having a pH in the range of about 8.0-11.0 and a second part of a water-compatible or water-soluble bifunctional crosslinking agent. When the two parts of the mixture are combined, the mixture is initially a liquid which cures in vivo on the surface of tissue in less than about one minute to give a strong, flexible, pliant substantive composition which bonds to the tissue and is absorbed in about four to sixty days. The adhesive composition may be used either to bond tissue, to seal tissue or to prevent tissue adhesions caused by surgery.

Abstract: This invention is related to an adhesive composition which may be used to bond or seal tissue in vivo. The adhesive composition is readily formed from a two component mixture which includes a first part of a protein, preferably a serum albumin protein, in an aqueous buffer having a pH in the range of about 8.0-11.0 and a second part of a water-compatible or water-soluble bifunctional crosslinking agent. When the two parts of the mixture are combined, the mixture is initially a liquid which cures in vivo on the surface of tissue in less than about one minute to give a strong, flexible, pliant substantive composition which bonds to the tissue and is absorbed in about four to sixty days. The adhesive composition may be used either to bond tissue, to seal tissue or to prevent tissue adhesions caused by surgery.

Abstract: The present invention relates to the preparation and use of liquid formulations of plasma proteins, particularly blood coagulation factors. More specifically, the present invention relates to stable liquid formulations of Factor VIII and Factor IX that can be administered by injection or infusion to provide a constant level of the coagulation factor in the blood.