Abstract: A method for preparing human serum albumin comprises the step of heat-treating a human serum albumin solution containing contaminants at a pH value in the proximity to the isoelectric point of the contaminants.

Abstract: A process for the partial or complete separation of glycosylated and nonglycosylated proteins is described, in which: a) a triazine dye immobilized on a matrix is incubated with a mixture of glycosylated and nonglycosylated proteins, b) the matrix is then washed to remove the unbound proteins, and c) the proteins are eluted by means of a stepwise or continuous increase in the ionic strength or in the pH, nonglycosylated proteins and proteins having an increasing degree of glycosylation being collected separately from one another in the eluate fractions obtained. By means of the use of this process it is possible, for example, to prepare a human albumin which is free of glycoside bonds and is expressed in yeast cells.

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: Method for a continuous recirculating peritoneal dialysis wherein the peritoneal dialysis fluid is infused into a peritoneal cavity of a patient and then, typically on a continuous process basis a portion of the dialysis fluid is sequentially drained from the cavity, cleansed through an extracorpreal dialyzer, and reinfused into the cavity. The dialysis fluid contains as an osmotic agent a substance which does not substantially permeate through pores of hollow fiber membrane of an extracorporeal dialyzer, preferably an osmotic agent having a molecular weight of about 20,000 to about 100,000. The supplemented amount of the osmotic agent is reduced or not needed during the dialysis.

Abstract: A method for the concurrent purification and isolation of albumin and IgG from a fluid composition containing up to about 15%, by weight, of blood plasma proteins obtained from a plasma source that has not previously undergone any prior fractionation. In this method, the composition is buffered and thereafter modified by the addition, relative to IgG, of a thermal stabilization effective amount of a polyhydric alcohol, and, by addition, relative to albumin, of a thermal stabilization effective amount of a carboxylic acid (e.g. carboxylic acid having about 3 to about 10 carbon atoms), or the physiologically acceptable salt of said. The resulting fluid composition is thereafter heated to and maintained at a temperature in the range sufficient to effect essentially complete denaturation of proteins, other than the albumin and the IgG components, of said composition.

Abstract: Recombinantly produced serum albumin is purified in a series of steps, optionally by incubation with an anion-exchange adsorbent, followed by affinity chromatography employing a hydrophobic solid phase and using a water-soluble lipid anion as desorbens in the aqueous phase. Said immobile phase comprises a carrier coupled to a 2-mercapto or 2-hydroxy alkanoic acid.

Abstract: A protein polymer is soluble in aqueous media and retains the native ligand binding properties of the protein. The polymer comprises two or more protein monomer units, such as albumin molecules, that are covalently bound through coupling agents that give rise to spacer chains of atoms between the protein molecules. The spacer chains preferably have a length of at least twenty atoms. The protein polymers are suitable for pharmaceutical drug delivery of physiologically active molecules by a variety of routes.

Abstract: This invention relates to a conjugate which consists of an active substance and a native protein which is not regarded as exogenous and distinguish itself in that an intracellulary cleavable linker is present between the active substance and the protein. In addition, this invention concerns a process for the preparation of such a conjugate and its use.

Abstract: A modified serum albumin is provided which has been modified in the n-terminal region or binding region VI, such as through a truncation of at least one amino acid at the n-terminal end, so that it exhibits reduced or eliminated binding of trace metals such as nickel and/or copper. Other suitable modifications to this binding region include mutations such as an elongation or insertion which will be sufficient to disrupt the trace metal binding which is highest at this site. The modified albumin of the present invention is advantageous in that it is binding to trace metals is reduced or eliminated, and it can thus be used more safely and effectively than unmodified albumin with a reduced or eliminated likelihood of causing an allergic reaction to the trace metal in the human being treated with the albumin composition.

Abstract: The present invention relates to methods and compositions for use in treating cardiovascular disease and other inflammatory disorders that are augmented by C-reactive protein. More particularly, the invention relates to methods for screening for modulators that inhibit C-reactive protein and the use of these modulators to inhibit C-reactive protein induced vascular inflammation.

Abstract: A technique for forming conjugates of proteins and oligonucleotides is disclosed in which conjugation is performed while the oligonucleotide is attached to support media such as glass beads. The conjugated product may then be readily removed from the support media. Also disclosed are the conjugated products formed by this technique. The present invention is particularly directed to conjugates of albumin proteins and specifically to bovine serum albumin (BSA).

Abstract: A method is disclosed for separating a polypeptide monomer from a mixture comprising dimers and/or multimers. The method comprises applying the mixture to either a cation-exchange chromatography resin or an anion-exchange chromatography resin and eluting the mixture at a gradient of about 0-1 M of an elution salt, wherein the monomer is separated from the dimers and/or multimers present in the mixture.

Abstract: An exogenous pharmaceutical preparation in which a lipid tagged bioactive material is combined with albumin is disclosed. The albumin has a low proportion of lipidic/fatty acid groups (a molar ratio of fatty acid groups to albumin of less than 0.7) and is preferably fatty acid free. The albumin may be naturally extracted such as Human Serum Albumin or recombinantly produced. A range of bioactive substances, such as peptides, proteins or vaccines may be tagged and combined with albumin for human, veterinary or agricultural use. Several antimicrobial peptides are disclosed. Binding to the albumin mediates the biostability of the tagged bioactive material. Due to this stabilization, the antimicrobial activity of a model lipopeptide is enhanced when combined with substantially fatty acid free-albumin. When bound to albumin, therefore, the model lipopeptide exerts an antimicrobial effect at a lower concentration than the model lipopeptide alone.

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: Biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.

Abstract: Biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.

Abstract: The present invention provides compositions comprising biologically-active somatotropin formulated for extended release and methods of preparing and methods of using the same. These compositions comprise somatotropin, at least a first bioavailability-enhancing constituent (BEC), and a substantially non-aqueous, hydrophobic excipient, and optionally a second BEC. The first BEC is typically a surfactant (preferably a non-ionic surfactant) or a cyclodextrin compound. The optional second BEC may comprise (i) amino acids or amino acid derivatives; (ii) hydroxamate derivatives; (iii) non-reducing carbohydrates; (iv) oxo-acid salts; or (v) a mixture of two or more compounds from within the foregoing classes (i)-(iv).

Abstract: The present invention provides compositions which allow for the extended release and enhanced bioavailability of biologically-active polypeptides following parenteral delivery to an animal. More particularly, it concerns compositions comprising biologically-active somatotropin formulated for extended release, methods of preparing these compositions, and methods of using the same. These compositions comprise somatotropin, a bioavailability-enhancing constituent (BEC), and a substantially non-aqueous, hydrophobic excipient. The BEC may comprise (i) amino acids or amino acid derivatives, such as histidine-HCl; (ii) hydroxamate derivatives, such as histidine hydroxamate or suberohydroxamic acid; (iii) non-reducing carbohydrates, such as trehalose or trehalose octaacetate; (iv) oxo-acid salts, such as a mixture of monobasic and dibasic sodium phosphate; or (v) a mixture of two or more compounds from within the foregoing classes (i)-(iv).

Abstract: Compositions, kits and methods are provided for promoting general health or for prevention or treatment of diseases by using novel recombinant fusion proteins of human serum albumin (HSA) and bioactive molecules. The bioactive molecules may be a protein or peptide having a biological function in vitro or in vivo, and preferably, having a therapeutic activity when administered to a human. By fusing the bioactive molecule to HSA, stability of the bioactive molecule in vivo can be improved and the therapeutic index increased due to reduced toxicity and longer-lasting therapeutic effects in vivo. In addition, manufacturing processes are provided for efficient, cost-effective production of these recombinant proteins in yeast.

Abstract: The present invention relates to glucagon-like-1 compounds fused to proteins that have the effect of extending the in vivo half-life of the peptides. These fusion proteins can be used to treat non-insulin dependent diabetes mellitus as well as a variety of other conditions.

Abstract: A method is provided for removing citrate, aluminum, and other multivalent ions and contaminants from proteins by adjusting the pH of a solution containing the protein to a pH from about 7 to about 10, and diafiltering the pH-adjusted solution against aqueous solutions which have a low level of ions.

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disordrs or conditions using albumin fusion proteins of the invention.

Abstract: Materials, methods, and compositions for making crosslinked albumin hydrogels are included in the application. Embodiments include a biocompatible material of albumin crosslinked with an n-functional crosslinking agent wherein n is at least 3. Other embodiments include a cross-linking agent having a polyalkylene oxide member. Other embodiments include a system for administering an albumin material, the system having albumin and a crosslinking agent that reacts with the albumin to form a crosslinked material made of crosslinked albumin. Another embodiment is a method of making a biocompatible material that includes a step of mixing albumin with an n-functional crosslinking agent wherein n is at least 3.

Abstract: The subject invention relates to a conjugate which may be used for the detection of an analyte in a test sample. In particular, the conjugate comprises a heterophilic carrier, at least 10 label groups, an analyte-specific binding pair member (e.g., an antibody or antigen with complexes with the antigen or antibody of interest, respectively) as well as a heterophilic linker which indirectly attaches the acridinium-containing compounds to the analyte-specific binding pair member.

Abstract: The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event.

Abstract: The present invention relates to a process for purifying the protein human serum albumin extracted from serum or recombinant human albumin produced by transforming a microorganism with a nucleotide coding sequence encoding the amino acid sequence of human serum albumin. The present invention provides highly purified albumin.

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disordrs or conditions using albumin fusion proteins of the invention.

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disordrs or conditions using albumin fusion proteins of the invention.

Abstract: The invention provides a process for purifying recombinant human serum albumin (rHSA) by heating a-culture medium containing rHSA and the rHSA-producing host cells, feeding said heated solution upwardly into a fluidized bed in which adsorbent particles are suspended to effect contacting with the adsorbent particles and then recovering the adsorbed fraction containing the rHSA, and a composition comprising rHSA which shows a A350/A280 ratio of below 0.015, when formulated into a 25% solution of said albumin.

Abstract: A method for removing a serum albumin from a mixture of other compounds by contacting said mixture with a ligand a) having affinity for and enabling selective binding of the serum albumin and b) being attached to a base matrix insoluble in the aqueous media used or being possible to attach to such a matrix after having become bound to the serum albumin, characterized in that said ligand is derived from an albumin binding bacterial cell surface receptor and that the ligand lacks the IgG-binding and/or &agr;2-macroglobulin-binding ability found in native forms of these type of bacterial receptors. An albumin-binding ligand derived from a cell surface bacterial receptor and attached covalently to a carrier matrix, characterized in that the ligand is monovalent with respect to ability to bind a serum albumin. A method for removal of serum albumin from a sample that is to be assayed for non-serum albumin components.

Abstract: Cyclosporine derivatives are disclosed which possess enhanced efficacy and reduced toxicity over naturally occurring and other presently known cyclosporins and cyclosporine derivatives. The cyclosporine derivatives of the present invention are produced by chemical and isotopic substitution of the cyclosporine A (CsA) molecule by: (1) Chemical substitution and optionally deuterium substitution of amino acid 1; and (2) deuterium substitution at key sites of metabolism of the cyclosporine A molecule such as amino acids 1, 4, 9. Also disclosed are methods of producing the cyclosporine derivatives and method of producing immunosuppression with reduced toxicity with the disclosed cyclosporine derivatives.

Abstract: Conjugates are prepared from antinociceptive agents, particularly opioids or opioid analogs, more particularly dynorphins, endorphins, deltorphins, enkephalins or analogs thereof, by combining said antinociceptive agent with a material providing a functionally reactive group capable of reacting with a blood component (preferably a blood cell or protein). Said conjugates permit extension of the therapeutic life of the antinociceptive agent. They may be administered to patients to alleviate pain, produce analgesic effects, or assist in cases of narcotics withdrawal, and may also be used as probes for receptor activity. The administration to the patient may be made either in vivo or ex vivo and may be performed by either introducing the derivative including the reactive functional group into the patient's vascular system or preparing such a conjugate externally (or in vitro) and introducing that conjugate to the patient's vascular system.

Abstract: Conjugates are prepared from antinociceptive agents, particularly opioids or opioid analogs, more particularly dynorphins, endorphins, deltorphins, enkephalins or analogs thereof, by combining said antinociceptive agent with a material providing a functionally reactive group capable of reacting with a blood component (preferably a blood cell or protein). Said conjugates permit extension of the therapeutic life of the antinociceptive agent. They may be administered to patients to alleviate pain, produce analgesic effects, or assist in cases of narcotics withdrawal, and may also be used as probes for receptor activity.

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disordrs or conditions using albumin fusion proteins of the invention.

Abstract: The present invention is generally directed to the discovery of homocysteinylated proteins and its importance as an indicator of diseased states. In preferred embodiments of the present invention the isolation, detection, and use of homocysteinylated transthyretin are also provided. More preferably, detection and isolation of a homocysteinylated transthyretin complex from a biological fluid is provided in the present invention, as well as methods and compositions utilizing homocysteinylated transthyretin in the detection of homocysteine or elevated levels of homocysteine. More particularly, the present invention is directed to homocysteinylated transthyretin and its use as a marker for the diagnosis of homocysteinemia, hyperhomocysteinemia, and diseases associated therewith.

Abstract: The invention relates to a photoactivatable compound comprising a support molecule chosen from carbon-containing and/or sulfur-containing and/or nitrogen-containing and/or phosphorus-containing nonpolymer compounds, polymers and oligomers and to which are covalently bonded at least two species containing chemical groups which, after irradiation between 200 et 450 nm, are converted into reactive species capable of reacting with chemical groups belonging to other molecules. The invention also relates to a cosmetic composition comprising at least one photoactivatable compound according to the invention, and also to a cosmetic treatment process using this composition.

Abstract: A method for formulating and immobilizing a protein and a protein matrix formed by the method. The protein matrix preparation method results in a physically and chemically stable protein matrix that has low swelling, non-leaching, high activity, and high mechanical strength properties. The method includes cross-linking and hardening the protein mixture and using a mold to form a protein into a desired shape and size.

Abstract: A recombinant DNA molecule coding for a protein expressed by a Staphylococcus aureus bacterium, comprising the nucleotide sequence SEQ ID NO:1 or a homologous sequence, or a partial or homologous sequence of SEQ ID NO:1 coding for a polypeptide fragment comprising at least 15 amino acid residues, is described. Further, a protein expressed by such a bacterium or a polypeptide fragment comprising at least 15 amino acid residues, comprising the amino acid sequence SEQ ID NO:2 binds IgG and apolipoprotein H. Examples of the polypeptide fragments comprise the SEQ ID NO:3 through 6. These proteins and polypeptide fragments may be coupled to an inert carrier or matrix. Vectors comprising such a DNA molecule or the corresponding RNA molecule, and antibodies specifically binding to a polypeptide having an amino acid sequence of SEQ ID NO:4 or SEQ ID NO:6, are also disclosed.

Abstract: Biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.

Abstract: The invention features methods of purifying human serum albumin (hSA) from endogenous serum albumin of the host cell producing the hSA. The methods include providing a sample comprising hSA and serum albumin of the host cell, applying the sample to an affinity column that binds hSA at a higher affinity than the serum albumin of the host cell, eluting bound hSA from the affinity column, and crystallizing the eluted has. The invention also features compositions comprising hSA produced by the methods of the invention.

Abstract: A method for converting a multimer of human serum albumin into monomers thereof comprises the step of treating the multimer with an alkaline solution. This method permits the efficient and quite simple conversion of human serum albumin multimers into monomers thereof at a low cost.

Abstract: Recombinantly produced serum albumin is purified in a series of steps, optionally by incubation with an anion-exchange adsorbent, followed by affinity chromatography employing a hydrophobic solid phase and using a water-soluble lipid anion as desorbens in the aqueous phase. Said immobile phase comprises a carrier coupled to a 2-mercapto or 2-hydroxy alkanoic acid.

Abstract: Conjugates are prepared from antinociceptive agents, particularly opioids or opioid analogs, more particularly dynorphins, endorphins, deltorphins, enkephalins or analogs thereof, by combining said antinociceptive agent with a material providing a functionally reactive group capable of reacting with a blood component (preferably a blood cell or protein). Said conjugates permit extension of the therapeutic life of the antinociceptive agent. They may be administered to patients to alleviate pain, produce analgesic effects, or assist in cases of narcotics withdrawal, and may also be used as probes for receptor activity. The administration to the patient may be made either in vivo or ex vivo and may be performed by either introducing the derivative including the reactive functional group into the patient's vascular system or preparing such a conjugate externally (or in vitro) and introducing that conjugate to the patient's vascular system.

Abstract: A method for preparing human serum albumin comprises the step of heat-treating a human serum albumin solution containing contaminants at a pH value in the proximity to the isoelectric point of the contaminants.

Abstract: A process for the preparation of a protein solution is described which is not prone to flock or particle formation even on heat treatment, the heat treatment being carried out in a glass vessel which has been rinsed out beforehand with a detergent solution and then with distilled water or another detergent-free solvent.

Abstract: According to the present invention, methods and compositions are provided for spray-dried, interferon-based dry powder compositions, particularly interferon-beta. The compositions are useful for treating conditions in humans that are responsive to treatment with interferons. In particular, the methods of the present invention rely on spray drying to produce stable, high-potency dry powder formulations of interferons, including but not limited to IFN-beta. Surprisingly, it has been found that IFN can be prepared in high potency, dry powder formulations by spray drying. Such dry powder formulations find particular utility in the pulmonary delivery of IFN.

Abstract: Biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a variant thereof, methods for the preparation thereof, nucleotide sequences encoding such fusion polypeptides, expression cassettes comprising such nucleotide sequences, self-replicating plasmids containing such expression cassettes, and pharmaceutical compositions containing said fusion polypeptides.

Abstract: A peritoneal dialysis fluid used for a continuous recirculating peritoneal dialysis wherein the peritoneal dialysis fluid is infused into a peritoneal cavity of a patient and then, typically on a continuous process basis a portion of the dialysis fluid is sequentially drained from the cavity, cleansed through an extracorpreal dialyzer, and reinfused into the cavity. The dialysis fluid contains as an osmotic agent a substance which does not substantially permeate through pores of hollow fiber membrane of an extracorporeal dialyzer, preferably an osmotic agent having a molecular weight of about 20,000 to about 100,000. The supplemented amount of the osmotic agent is reduced or not needed during the dialysis.

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.