Abstract: The present invention relates to a CRH formulation having improved stability/efficacy. The improved CRH formulation is particularly suitable for treatment of various disorders. The invention also relates to a method of producing the CRH formulation, and to methods of treatment using said CRH formulation.

Abstract: Disclosed is a diagnostic marker for lung cancer comprising Hp?R as an active ingredient. Because blood, which is relatively easy to sample, is employed as a specimen, the diagnostic kit and marker for lung cancer is very simple and does not subject patients to a load compared to conventional methods that are directed to a biopsy. In addition, the kit and marker of the present invention is useful in the early diagnosis of lung cancer thanks to its high diagnostic sensitivity and selectivity.

Abstract: A method for analyzing secretome, a biomarker for lung cancer metastasis, and a siRNA compound for inhibiting lung cancer metastasis are disclosed. The method for analyzing secretome of the present invention comprises the following steps: (A) collecting proteome secreted from a cell; (B) providing a purification gel, wherein the purification gel comprises a low-density layer, and a high-density layer, and the low-density layer is stacked on the high-density layer; (C) adding the proteome on the low-density layer, and separating the proteome through the low-density layer and the high-density layer of the purification gel; (D) collecting the separated proteome on the interface between the low-density layer and high-density layer, and tagging the separated proteome with a reagent after digestion; and (E) analyzing the separated proteome tagged with the reagent, and comparing an analysis result with a proteomic database.

Abstract: The invention is directed to a method of removing a deleterious substance bound to a protein in blood of a patient by introducing a displacer substance into the blood under conditions in which the displacer substance replaces deleterious substance bound to the protein, thereby resulting in additional unbound deleterious substance in the blood, and removing unbound deleterious substance from the blood by extracorporeal renal replacement treatment.

Abstract: A previously unrecognized fundamental property of ?1PI is to regulate the phenotypic composition of circulating and tissue-associated cells derived from hematopoietic stem cells. The present invention comprises screening for various unmodified and modified ?1PI's which are useful in the treatment of abnormalities in the number of cells of myeloid or lymphoid lineage that are associated with HW-1 infection, microbial infection, leukemia, solid tumor cancers, atherosclerosis, autoimmunity, stem cell transplantation, organ transplantation, and other diseases affected by cells of the immune system. The interaction of ?1PI with its receptors, HLECS and LRP, influences the level of cells of different lineages. Genetic and proteolytic modification of ?1PI is used to target these receptors to increase or decrease specific cell populations, as needed, in the various disease states.

Abstract: The present invention relates to a method of modifying serine protease inhibitors in order to acquire or enhance any one of a variety of desired properties, including extent of inhibition, maintenance of inhibition following cleavage of the serine protease inhibitor by the target serine protease, speed of binding to the serine protease, neutralisation, and binding affinity. The present invention also relates to the products of such modifications and the uses of such products, in particular, their use in therapy.

Abstract: Methods are described for improvement of the serum half life of therapeutic nucleic acids by 3? conjugation to useful target proteins, or other large molecules with useful function. In one embodiment, a 3? A, C or G overhang is added to ds-DNA and the primary amines conjugated using biocompatible bifunctional linkers to proteins. The resulting nucleic acid-3? conjugates are serum nuclease-resistant and retained in vivo for long periods without rapid kidney clearance. Further, the choice of conjugate imparts additional functionality to the nucleic acid-3? conjugate.

Abstract: A molecule which recognises holo-DBP but which does not recognise apo-DBP or has relatively low affinity thereto.

Abstract: The present invention relates to a drug delivery system for use in the treatment of vascular and vessel-related pathologies, comprising a drug delivery platform that comprises at least one compound capable of exerting an effect on the formation and/or maintenance of a thrombus in the vessel to be treated. The platform is preferably formed by liposomes that are sterically stabilized by grafting of poly(ethylene glycol) onto the liposome surface. The liposomes may further comprise photosensitizers and targeting molecules. The liposomes may be thermosensitive. The compound is suitably tranexamic acid. The drug delivery system is preferably used for the treatment of port wine stains.

Abstract: Use of a mutated antithrombin having substantially no activity, in particular no anticoagulant activity, possibly in association with an anticoagulant, for the preparation of a drug intended for the prevention or treatment of pathologies linked to or associated with coagulation disorders.

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).

Abstract: A method of indirectly determining D/P creatinine for easily judging a peritoneal function is provided that does not require blood sampling or multiple recoveries of dialysis effluent. The method includes preparing a dialysis effluent obtained by peritoneal dialysis, measuring at least one protein marker selected from the group consisting of prealbumin, haptoglobin, alpha 1-microglobulin, C4, and total protein that are contained in the dialysis effluent, and determining D/P creatinine indirectly from the correlation equation that represents the relationship between the marker concentration and the D/P creatinine value that has been prepared beforehand. Furthermore, the PET category is determined indirectly from the D/P creatinine, which has been determined indirectly, based on the known reference value.

Abstract: Haptoglobin (Hp) removes cell-free Hemoglobin (Hb), with different physiological effects depending on the particular Hp polymer. We propose that material enriched for alpha 1 chain Hp polymeric forms, such as those made from Cohn fraction V precipitate, will be more suitable for the treatment of certain diseases benefiting from both an antioxidant and anti-inflammatory component, such as for hemolytic disease. Material enriched for alpha-2 chain Hp polymeric forms, made for example from Cohn fraction IV precipitate, will be more suitable for treatment of diseases where an angiogenic, and/or inflammatory affect, and/or limited extravasation is desirable.

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: 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 invention provides a method for diagnosing Kawaski Disease (KD) in a patient suspected of suffering from KD by using as an index a ratio of the level (by weight/volume, w/v) of haptoglobin (Hp) to the level (by weight/volume, w/v) of apolipoprotein A1 (Apo A1) in a patient. A system for use with the method is also included. In addition, the invention also provides a method for diagnosing Atypical Kawasaki Disease (AKD) in a patient suspected of suffering from KD by identifying the phenotype of haptoglobin in said patient and correlating the presence of Hp2-1 or Hp1-1 haptoglobin phenotype with AKD and providing immediate treatment of the patient.

Abstract: This invention relates to transgenically produced human Antithrombin III (tgATIII). The human ATIII produced by the transgenic process of the present invention has a monosaccharide composition which comprises N-acetylgalactosamine (GaINAc) along with fucose, N-acetylglucosamine, galactose, mannose, and N-acetylneuraminic acid/N-glycolyneuraminic acid. The monosaccharide composition differs with that of plasma derived ATIII (phATIII). It has been found that tgATIII has an increased clearance rate when compared to phATIII.

Abstract: A peptide according to the present invention is not more than 40 amino acids long and contains a sequence which is at least 6 amino acids long from the amino acid partial sequence between the amino acids 144 and 183 of human .alpha.1-microglobulin or/and a sequence which is at least 6 amino acids long from the amino acid partial sequence between the amino acids 1 and 20 of human .alpha.1-microglobulin.An antibody according to the present invention is capable of specific binding to a peptide according to the present invention as well as to human .alpha.1-microglobulin.In order to determine human .alpha.1-microglobulin in a sample liquid by an immunoassay, the sample liquid is brought into contact simultaneously or sequentially with defined amounts of the components antibody and peptide whereby one of the components is labelled and the determination is carried out by means of this label.

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: The present invention is directed to a process for purifying alpha-1-PI. The process comprises providing an impure protein fraction which comprises alpha-1-PI. The impure protein fraction is suspended in an aqueous solution at pH 6. Insoluble proteins are recovered and resuspended in aqueous solution at pH 8.5. PEG is added to precipitate .alpha.-2 proteins. To the PEG supernatant precipitation, which comprises alpha-1-PI, is added ZnCl.sub.2 to precipitate crude alpha-1-PI. The crude alpha-1-PI is resolubilized and applied to an anion-exchange medium. A fraction comprising alpha-1-PI is recovered from the anion-exchange medium. Alpha-1-PI purified by the process has a specific activity about 1.0 units/OD.sub.280.

Abstract: This invention relates to transgenically produced human Antithrombin III (tgATIII). The human ATIII produced by the transgenic process of the present invention has a monosaccharide composition which comprises N-acetylgalactosamine (GaINAc) along with fucose, N-acetylglucosamine, galactose, mannose, and N-acetylneuraminic acid/N-glycolyneuraminic acid. The monosaccharide composition differs with that of plasma derived ATIII (phATIII). It has been found that tgATIII has an increased clearance rate when compared to phATIII.

Abstract: Virus inactivating chemicals and/or detergents in an aqueous composition containing a water-soluble plasma protein are reduced by selecting a suitable combination of temperature and concentration above 0.5M of salt with a high salting out effect according to the Hofmeister series, thereby forming vesicles containing the virus inactivating chemical and/or detergent. These vesicles are removed from the aqueous phase, e.g. by phase separation or filtration, and the protein thereafter isolated from the aqueous phase. The water-soluble plasma protein can be e.g. antithrombin III, transferrin or albumin. When the aqueous phase comprises e.g. a salt of citrate or sulphate in a concentration above 1M at room temperature, the reduction of virus inactivating chemical or detergent can be as high as 2000 times or more, giving a final concentration below 5 ppm.

Abstract: The present invention is directed to a process for purifying alpha-1-PI. The process comprises providing an impure protein fraction which comprises alpha-1-PI. The impure protein fraction is suspended in an aqueous solution at pH 6. Insoluble proteins are recovered and resuspended in aqueous solution at pH 8.5. PEG is added to precipitate .alpha.-2 proteins. To the PEG supernatant precipitation, which comprises alpha-1-PI, is added ZnCl.sub.2 to precipitate crude alpha-1-PI. The crude alpha-1-PI is resolubilized and applied to an anion-exchange medium. A fraction comprising alpha-1-PI is recovered from the anion-exchange medium. Alpha-1-PI purified by the process has a specific activity about 1.0 units/OD.sub.280.

Abstract: Cation chromatography with solutions at pH less than 6.0 and low ionic strength can be utilized to purify human .alpha.-1 proteinase inhibitor (.alpha.-1 PI) from biological fluids including plasma and plasma fractions. The cation chromatography takes advantage of the fact that active .alpha.-1 PI does not bind to the cation column under these conditions but other proteins, including denatured .alpha.-1 PI and albumin, do. The effect is that active .alpha.-1 PI flows through the chromatography column leaving the contaminating proteins behind. Recovery of .alpha.-1 PI is high and improvement of purity is dramatic.

Abstract: There is provided a method for treating tumors in mammals by the administration of alpha 1-antitrypsin alone or in combination with other protease inhibitors.

Abstract: Polymeric carriers are polypeptides comprising at least one drug-binding domain that non-covalently binds a drug. A polymeric carrier may be attached to an antibody specific for desired target cells to form immunoconjugates that deliver a drug to the target cells in vivo. A polymeric carrier may be attached to a proteinaceous or a non-proteinaceous ligand or anti-ligand to form a conjugate useful in pretargeting protocols to deliver a drug to target cells in vivo. The carriers are derived from drug-binding proteins and produced through peptide synthesis or recombinant DNA technology.

Abstract: Polymeric carriers are polypeptides comprising at least one drug-binding domain that non-covalently binds a drug. A polymeric carrier may be attached to an antibody specific for desired target cells to form immunoconjugates that deliver a drug to the target cells in vivo. The carriers are derived from drug-binding proteins and produced through peptide synthesis or recombinant DNA technology.

Abstract: Methods are disclosed for increasing the solubility of antibodies and their radioisotope, toxin, or drug immunoconjugates and for reducing the non-specific uptake of antibody, either conjugated or unconjugated, into the RES organs such as via Fc receptor-mediated mechanisms. The methods involve incubation of the reactive component with amphipathic molecules, such as an anionic detergent, to achieve the desired result. A preferred anionic detergent in this regard is sodium dodecylsulfate.

Abstract: A method of fractionating plasma protein which comprises treating a plasma protein-containing material in the following sequence of steps, provided that steps (ii) through (v) may be performed in an optional order: (i) freeze-thaw treatment, (ii) treatment at 5 to 10% ethanol concentration, (iii) treatment with an anion exchanger, (iv) affinity chromatography with immobilized lysine, (v) affinity chromatography with immobilized heparin, (vi) treatment at 18 to 30% ethanol concentration, (vii) treatment at 35 to 45% ethanol concentration.

Abstract: A method for the prophylaxis or direct treatment of mast cell implicated skin inflammation in a patient which comprises topically administering an effective amount of an analog of alpha 1-antitrypsin, its salts or derivatives, and compositions thereof.

Abstract: Conjugates of transferrin or ceruloplasmin with anti-tumour agents. Such conjugates are useful in the treatment of tumours. Suitable anti-tumour agents include adriamycin, daunomycin, methotrexate, vincristin, 6-mercaptopurine, cytosine arabinoside and cyclophosphamide. Transferrin or ceruloplasmin in preferably coupled to the anti-tumour agent by means of glutaraldehyde.

Abstract: An agent for the therapy or prophylaxis of disturbances of hemostasis, which contains tissue protein PP4, a process for the purification of PP4 by means of a hydrophobic adsorbent which is insoluble in water, and a process for the pasteurization of a solution containing PP4 in the presence of calcium ions and of at least one mono- or oligosaccharide or sugar alcohol and, where appropriate, of an amino acid, and the use of PP4, are described.

Abstract: The present invention is concerned with novel monoclonal antibodies which define a glycolipid antigen associated with human non-small cell lung carcinomas ("NSCLC") and certain other human carcinomas. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods. The invention also comprises a method for determining the presence of a malignant condition in lung tissue and other human tissue. The method involves examining the human tissue for the presence of a glycolipid antigen having the characteristics of a ganglio-N-triosylceramide.

Abstract: A simple, rapid and reliable assay for measuring functional enzyme inhibitor levels in body fluids and tissues, especially functional .alpha..sub.1 -proteinase inhibitor levels in human plasma or serum. .alpha..sub.2 -Macroglobulin is first inactivated, then porcine pancreatic elastase incubated with the samples to form a complex between the elastase and the functional .alpha..sub.1 -PI. Deficient individuals are detected by the presence of a color change following addition of substrate. If desirable, residual enzyme activity can then be calculated and the .alpha..sub.1 -PI levels present in the original sample determined. The method provides a means for early screening of individuals with a genetic deficiency in circulating levels of .alpha..sub.1 -PI, thereby facilitating treatment and prevention of familial emphysema.

Abstract: Monoclonal antibodies to Mojave toxin and use for isolation of cross-reacting proteins in Crotalus venoms are disclosed. Hybridomas secreting monoclonal antibodies against Mojave toxin were established. The antibodies were used for identifying cross-reacting proteins in individual C. s. scutulatus and other Crotalus venoms and to isolate Mojave toxin. The antibodies recognized five bands with a pI range from 5.1 to 6.1 in immunoblots of electrofocused crude venom and Mojave toxin purified by immunoaffinity chromatography. The specificity of the antibodies was for the basic subunit of the toxin which resolved into four bands of pI between 9.3 and 9.6. Individual C. s. scutulatus venoms of snakes from Texas and southern Arizona had multiple bands with pI's ranging from 4.9 to 6.3. Cross-reacting proteins were also recognized by antibodies in the electrophoresed venoms of C. basiliscus, C. d. durissus, C. d. terrificus, C. h. horridus, and C. v.

Abstract: Substantially pure modified .beta..sub.2 -microglobulin (m.beta..sub.2 m) of the formula I ##STR1## wherein R.sub.1 is 24-amino acid residue, with the sequence Ile-Gln-Arg-Thr-Pro-Lys-Ile-Gln-Val-Tyr-Ser-Arg-His-Pro-Ala-Glu-Asn-Gly-Ly s-Ser-Asn-Phe-Leu-Asn, R.sub.2 is a 30-amino acid residue with the sequence Tyr-Val-Ser-Gly-Phe-His-Pro-Ser-Asp-Ile-Glu-Val-Asp-Leu-Leu-Lys-Asn-Gly-Gl u-Arg-Ile-Gly-Lys-Val-Glu-His-Ser-Asp-Leu-Ser, R.sub.3 is a 20-amino acid residue with the sequence Trp-Ser-Phe-Tyr-Leu-Leu-Tyr-Tyr-Glu-Phe-Thr-Pro-Thr-Glu-Lys-Asp-Glu-Tyr-Al a, R.sub.4 is a 19-amino acid residue with the sequence Arg-Val-Asn-His-Val-Thr-Leu-Ser-Gln-Pro-Lys-Ile-Val-Lys-Trp-Asp-Arg-Asp-Me t, X is Phe, Phe-Ser, or Phe-Ser-Lys, and Y is Asp, Lys-Asp, or Ser-Lys-Asp is disclosed. The presence of the protein in body fluids is a diagnostic and/or prognostic marker for the development of a variety of disorders such as different types of cancer and diseases involving the immune system. Also disclosed are specific anti-m.

Abstract: Noval abnormally glycosylated a.sub.2 -macroglobulins have been found in sera of patients suffering from autoimmune diseases. Such abnormally glycosylated materials have been isolated. The presence of these abnormally glycosylated materials in a patient's serum provides a means for diagnosing such diseases.

Abstract: A process for the purification of tissue protein PP4 which can be obtained from placenta is described.This process makes use of the property of binding to saccharide polysulfates or to sulfated sugars in the presence of calcium ions.

Abstract: Conjugates of transferrin or ceruloplasmin with anti-tumor agents. Such conjugates are useful in the treatment of tumors. Suitable anti-tumor agents include adriamycin, daunomycin, methotrexate, vincristin, 6-mercaptopurine, cytosine arabinoside and cyclophosphamide. Transferrin or ceruloplasmin is preferably coupled to the anti-tumor agent by means of glutaraldehyde.

Abstract: The administration of Factor I and/or Factor H to a mammal has been found to alleviate or prevent such autoimmune diseases as systemic lupus erythematosus, rheumatoid arthritis and glomerulonephritis.

Abstract: Parenteral solutions comprising(a) a sparingly soluble medicament active compound,(b) a solvent consisting of(i) 5-100 M/V % of an organic solvent or of a mixture of organic solvents and(ii) 0-95 W/V % of water,(c) A 0.5-30 W/V % strength aqueous solution of a human serum protein and customary auxiliaries and/or excipients, 1 to 40,000 parts by weight, preferably 25 to 30,000 parts by weight of solvent (b) and 1 to 1,000,000 parts by weight, preferably 50 to 40,000 parts by weight, of human serum protein solution (c) being present per part by weight of medicament active compound.The sparingly soluble medicament active compounds which can be used have a solubility in water of between 1 .mu.g and 10 g, preferably between 10 .mu.g and 1 g per liter of water. Examples of such medicaments are dihydropyridine compounds and pyrazolones, and muzolimine.

Abstract: High purity albumin can be recovered in high yield from human plasma protein solution containing albumin by heat-treatment of the solution to denature and precipitate non-albumin proteins in a combination of specific conditions such as protein concentration of the solution, pH, heating time and temperature, the concentration of precipitant ammonium sulfate.

Abstract: A fibronectin preparation in the form of an aqueous solution at least upon use is disclosed. The preparation contains at least one member selected from the group consisting of disaccharides, albumin and nonionic surface active agents as a stabilizer. The preparation has improved water-solubility when in use and high stability in an aqueous solution.

Abstract: Biological compositions are decontaminated by treatment with furocoumarin derivatives and irradiation under particular conditions in which the proteins retain their original physiological activities and any pathogenic microorganisms and polynucleotide fragments thereof are rendered inactive. It has been found that reduction of the amount of dissolved oxygen in the treatment solution substantially inhibits denaturation of the proteins.

Abstract: A fibronectin injectable solution is made by recovering a fibronectin-containing raw material which is solubilized, provided with stabilizers and then subjected to an initial heat treatment at 57.degree. to 60.degree. for at least ten hours. After fibronectin concentration and the addition of further stabilizers and plasma-protein vehicle, the solution is again subjected to a temperature of 60.degree. for ten hours to provide an injectable solution which is free from virulent hepatitis.

Abstract: Compositions containing therapeutically or immunologically active proteins are rendered substantially free from infectious agents such as viable viruses and bacteria without substantial loss of therapeutic or immunologic activity by mixing the protein composition with a complex formed from transition metal ions, such as copper ions, and an angularly-fused, polynuclear heterocyclic arene having two nitrogen atoms in a "cis-ortho" relationship, such as phenanthroline, and a reducing agent such as a thiol or ascorbic acid or ascorbate salt or mixtures of ascorbic acid or ascorbate with a thiol in amounts and at a temperature and for a time sufficient to inactivate substantially all of the viruses and bacteria contained therein. Compositions containing therapeutically active proteins substantially free from viral and bacterial infectivity, which have heretofore been unattainable, can be prepared by the method of the invention.

Abstract: What is disclosed is a method for isolating the cold insoluble globulin (CIG) from blood plasma concentrates containing factor VIII.

Abstract: There is disclosed an improved method for separating one of alpha-1-proteinase inhibitor (also known as alpha-1 antitrypsin) and antithrombin-III from an aqueous solution of plasma proteins containing the same, such as from Cohn Fraction IV-1, Cohn Fraction IV, reworks of Cohn Fraction IV and IV-1, Cohn Effluent II & III and Cohn Effluent I. The method includes the steps of first holding an aqueous solution of plasma proteins containing one of alpha-1-proteinase inhibitor and antithrombin-III in a relatively large volume of buffer solution as solvent and at a pH adjusted to be relatively basic when compared to conditions heretofore known, and at a temperature in the range of from 2.degree.-50.degree. C. for a period of about 0.2-24 hours. Following the above treatment, alpha-1-proteinase inhibitor and antithrombin-III are obtained by applying conventional techniques to the resulting solution. Accordingly, the solution is then mixed with a polyalkylene glycol, e.g.

Abstract: The drug such as antitumor agents or antibiotics can preferentially be carried to a morbid part, for example, injured tissue and tumor site by administering its complex with fibronectin combined through an oxidized dextran to repair the morbid part. The complex is prepared by reacting the drug, an oxidized dextran having a cleaved structure of aldohexopyranose ring, and fibronectin.