Abstract: Provided herein are methods of identifying a protein capable of binding a ligand, the method comprising: (a) contacting the ligand with two or more samples comprising a plurality of proteins in a solution; (b) separating the proteins bound to the ligand (“bound proteins”) from the proteins that are not bound to the ligand (“unbound proteins”) in each sample; (c) denaturing and digesting the bound proteins to form a plurality of peptides in each sample; (d) quantifying a plurality of molecular features contained in the plurality of peptides in each sample, wherein the molecular features are defined as having a mass to charge ratio, retention time, and peak intensity as measured by mass spectrometry; and (e) ranking the molecular features that exhibit a statistically significant difference in quantity between the samples contacted with the ligand and a sample that is not contacted with the ligand (“statistically significant molecular feature”).

Abstract: The present invention relates to an improved method of purifying an immunoglobulin, and more particularly to a method of purifying an immunoglobulin which is capable of sufficiently removing impurities from an immunoglobulin-containing plasma protein sample through a simple process, comprising a single anion-exchange chromatography and a single cation-exchange chromatography.

Abstract: The present invention is in the field of purification and protein purification in particular. The invention provides improved techniques for the industrial-scale purification of proteins and other biomolecules. More specifically, it relates to a process for the purification of a compound of interest, such as a protein, preferably an antibody or an antibody fragment using a chromatography step, preferably a semi-continuous chromatography step.

Abstract: A process for separating amino acids and peptides from raw and digested farm manure is disclosed. The raw manure may be recovered from sand bedding used in the cow stalls of some farms. The process involves the steps of precipitating out struvite and separating a stream rich in amino acids and peptides from a mineral rich stream in a dissolved air floatation machine. Struvite precipitation is accomplished by the addition of polydicyandiamide and an acrylate based polymer, while the separation of the stream rich in fibers, amino acids and peptides from a mineral rich streams is accomplished by the addition of an acrylamide chloride copolymer.

Abstract: IFN-alpha mutants are obtained by substituting Cys for Tyr at position 85 or 86 in existing IFN-alpha. Their polyethylene glycol derivatives with high in vitro antiviral activity and prolonged in vivo half-life are also provided, wherein a polyethylene glycol moiety is covalently bound to the free Cys residue of an IFN-alpha mutant. The preparation methods of PEG derivatives of IFN-alpha mutants and medical compositions comprising the derivatives are also provided. The test results showed that the IFN-alpha mutants of the present invention are ready to prepare and have high activity; their polyethylene glycol derivatives have extended lifetime in the body and low clearance rate.

Abstract: Disclosed are methods, compositions and kits for the isolation of exosomes from biological fluids and tissues. Volume-excluding polymers are used to precipitate exosomes from biological samples thereby allowing exosome isolation by low-speed (benchtop) centrifugation or filtration. Further fractionation of exosomes after precipitation is also described.

Abstract: The invention is a method for the purification of mono-PEGylated erythropoietin using two cation exchange chromatography steps wherein the same type of cation exchange material is used in both cation exchange chromatography steps and a method for producing a mono-PEGylated erythropoietin in substantially homogeneous form.

Abstract: A method for extracting water from an aqueous solution of a protein comprising the steps of: (a) intermixing the aqueous solution of the protein with a sufficient quantity of at least one glycol ether at a temperature at least 30 centigrade degrees above the lower critical solution temperature (LCST), preferably at least 20 centigrade degrees above the LCST, and most preferably at least 10 degrees above the LCST, to form a suspension comprising a concentrated aqueous protein phase and a liquid organic phase comprising said at least one glycol ether and at least 10 percent water extracted from the aqueous solution of the protein, wherein the glycol ether has an inverse solubility in water, with the proviso that the solubility of the glycol ether in water is significantly less than the solubility of water in the glycol ether, and the glycol ether does not significantly deactivate the protein, and (b) separating the concentrated aqueous protein phase formed in step (a) from at least a portion of the liquid orga

Abstract: Disclosed herein are compounds useful in the preparation non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are compound useful in the preparation of non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: Disclosed herein are compounds useful in the preparation of non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are compounds useful in the preparation of non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such resultant polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: Peptide-modified polyurethanes comprising the reaction product of an isocyanate, a chain extender, and a peptide are provided. Also provided processes for making a peptide-modified polyurethane comprising: providing an isocyanate; providing a chain extender; providing a peptide; and allowing the isocyanate, chain extender, and peptide to react thereby forming the peptide-modified polyurethane, as well as methods for treating a subject comprising: providing a peptide-modified polyurethane that comprises the reaction product of an isocyanate, a chain extender, and a peptide; and administering the peptide-modified polyurethane to the subject.

Abstract: This invention relates to novel protein conjugates, in particular, to novel pegylated proteins, and their methods of making and use. One aspect of the present invention relates to pegylated-erythropoietin having greater clinical efficacy and stability during shipment and storage than current erythropoietin formulations.

Abstract: The present invention relates to a selectively soluble polymer capable of binding to a desired molecules in an unclarified mixture containing various biological materials and the methods of using such a polymer to purify a molecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and/or salt concentration and is rendered insoluble and precipitates out of solution upon a change in the process conditions. The polymer is capable of binding to the desired molecule (protein, polypeptide, etc) and remains capable of binding to that molecule even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered such as by elution and further processed.

Abstract: Ligand functionalized substrates, methods of making ligand functionalized substrates, and methods of using functionalized substrates are disclosed.

Abstract: A composition comprising from about 0.001% to about 0.4% cyclosporin A, a surfactant, and an oil having a specific gravity from 0.8 to 0.95 is disclosed herein.

Abstract: The present invention relates to a selectively soluble polymer capable of binding to a desired molecules in an unclarified mixture containing various biological materials and the methods of using such a polymer to purify a molecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and/or salt concentration and is rendered insoluble and precipitates out of solution upon a change in the process conditions. The polymer is capable of binding to the desired molecule (protein, polypeptide, etc) and remains capable of binding to that molecule even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered such as by elution and further processed.

Abstract: The present invention relates to a liquid pharmaceutical composition comprising a granulocyte colony stimulating factor polypeptide conjugated with a polymer, the composition having a pH value in the range of 4.5 to 5.5. The composition further comprises a surfactant and optionally one or more other pharmaceutically acceptable excipients. Further, the composition of the invention is free from tartaric acid or salts thereof and from succinic acid and salts thereof as buffering agents and does not contain amino acids as stabilizer. The composition has a good storage stability and is especially useful for the prophylaxis and treatment of disorders and medical indications where granulocyte colony stimulating factor preparations are considered as useful remedies.

Abstract: An improved extractive reagent composition and method for extracting an immunosuppressant drug, such as sirolimus, tacrolimus or cyclosporine, from blood samples while yielding a test sample extract that has low vapor pressure and is compatible with immunoassay components. The inventive reagent composition comprises dimethyl sulfoxide (DMSO), at least one divalent metal salt and water. The sample extracts resulting from use of each of these combinations have low vapor pressure and are compatible with immunochemistry assays.

Abstract: The present invention concerns novel synthetic blocking reagents for the reduction of non-specific bindings in solid phase assays that rely on biological and specific recognition, e.g., in enzyme-linked immunosorbent assays (ELISAs). The invention provides the use of compounds as blocking reagents as well as kits comprising these compounds. The compounds comprise one or more poly(ethylene glycol) moieties, one or more alkyl- or aminoalkyl groups and another unit bridging the aforementioned groups, wherein the compound comprises at least one amino group.

Abstract: A method for producing a capsule for protein crystallization is provided. The method comprises adding a solution containing a protein and a gelling agent to an ionic cross-linking solution to form an ionically cross-linked gel capsule that encapsulates a solution of the protein.

Abstract: The invention relates to a method of dewatering corn gluten stream wherein coagulant is add to the corn gluten stream of the corn wet milling process. The method of dewatering corn gluten uses an effective amount of a coagulant of one or more anionic polymers, the anionic polymers comprising one or more anionic monomers. The method further includes a process for separating the water from the gluten using a solids/liquids filtration device.

Abstract: The present invention relates to a selectively soluble polymer capable of binding to a desired biomolecules in a mixture containing various biological materials and the methods of using such a polymer to purify a biomolecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and/or salt concentration and is rendered insoluble and precipitates out of solution upon a change in the process conditions. The polymer is capable of binding to the desired biomolecule (protein, polypeptide, etc) and remains capable of binding to that biomolecule even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered such as by elution and further processed.

Abstract: The present invention relates to a selectively soluble polymer capable of binding to one or more constituents in a mixture containing various biological materials and the methods of using such a polymer to purify a biomolecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and is rendered insoluble and precipitates out of solution upon a change in the process conditions. While in its solubilized state, the polymer is capable of binding to a selected entity within the stream such as impurities (DNA, RNA, host cell protein, endotoxins, etc) in a cell broth and remains capable of binding to that entity even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered and further processed.

Abstract: The present invention concerns methods and compositions for PEGylated complexes of defined stoichiometry and structure. Preferably, the PEGylated complex is formed using dock-and-lock technology, by attaching a therapeutic agent to a DDD sequence and a PEG moiety to an AD sequence, allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two therapeutic agents and one PEG moiety. Alternatively, the therapeutic agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one therapeutic agent. In more preferred embodiments, the therapeutic agent may comprise any peptide or protein of physiologic or therapeutic activity, preferably a cytokine, more preferably interferon-?2b. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: Ligand functionalized substrates, methods of making ligand functionalized substrates, and methods of using functionalized substrates are disclosed.

Abstract: The present invention relates to a selectively soluble polymer capable of binding to a desired biomolecules in a mixture containing various biological materials and the methods of using such a polymer to purify a biomolecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and/or salt concentration and is rendered insoluble and precipitates out of solution upon a change in the process conditions. The polymer is capable of binding to the desired biomolecule (protein, polypeptide, etc) and remains capable of binding to that biomolecule even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered such as by elution and further processed.

Abstract: A substrate comprising a crosslinked polymer primer layer, and grafted thereto a ligand-functionalized polymer is provided. The grafted polymer has the requisite affinity for binding neutral or negatively charged biomaterials, such as cells, cell debris, bacteria, spores, viruses, nucleic acids, and proteins, at pH's near or below the pI's of the biomaterials.

Abstract: IFN-alpha mutants are obtained by substituting Cys for Tyr at position 85 or 86 in existing IFN-alpha. Their polyethylene glycol derivatives with high in vitro antiviral activity and prolonged in vivo half-life are also provided, wherein a polyethylene glycol moiety is covalently bound to the free Cys residue of an IFN-alpha mutant. The preparation methods of PEG derivatives of IFN-alpha mutants and medical compositions comprising the derivatives are also provided. The test results showed that the IFN-alpha mutants of the present invention are ready to prepare and have high activity; their polyethylene glycol derivatives have extended lifetime in the body and low clearance rate.

Abstract: The present invention relates to a selectively soluble polymer capable of binding to one or more constituents in a mixture containing various biological materials and the methods of using such a polymer to purify a biomolecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and is rendered insoluble and precipitates out of solution upon a change in the process conditions. While in its solubilized state, the polymer is capable of binding to a selected entity within the stream such as impurities (DNA, RNA, host cell protein, endotoxins, etc) in a cell broth and remains capable of binding to that entity even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered and further processed.

Abstract: Compounds comprising a peptide moiety, a linker moiety and a water-soluble polymer moiety such as a poly(ethylene glycol) moiety are disclosed. Various linker moieties for use in these compounds are also disclosed, along methods for their synthesis.

Abstract: Novel exendins with modifications at one or more of following positions: 2, 14, 27 or 28 and polyethylene glycol derivatives thereof are provided. These compounds are useful in treating type 2 diabetes as GLP-1 receptor agonists.

Abstract: The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are not involved in the binding of the ligand to the receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the amino acid sequences of regions of cytokine receptor ligands that are generally located on or within the region of the ligand protein that is opposite of the receptor complex, i.e., are generally derived from amino acid sequences of regions of the ligand protein that face away from the receptor complex while the ligand is bound to the receptor.

Abstract: The invention relates to an aqueous two phase extraction (ATPE) augmented precipitation process, which may be used to recover and also partially purify therapeutic proteins, including monoclonal antibodies from a crude multi-component mixture. The process involves the formation of a forward extraction PEG-Phosphate ATPE system in which the target product is preferentially partitioned to the polymer rich phase. A second ATPE back extraction system is then formed by introducing the polymer rich phase from the forward extraction to a new phosphate salt rich phase, causing the product to precipitate at the interface between the two phases. This precipitate is then recovered and resolubilised in a suitable buffer and may be passed on for further purification.

Abstract: Ligand functionalized substrates, methods of making ligand functionalized substrates, and methods of using functionalized substrates are disclosed.

Abstract: Methods are presented for isolating and purifying proteins by adding a polyelectrolyte to a cell culture fluid, such as a harvested cell culture fluid, and precipitating a protein-polyelectrolyte complex or a complex of impurities and the polyelectrolyte.

Abstract: The invention relates to a process for the purification of IL-18 binding protein (IL-18BP) from a fluid using aqueous two-phase partitioning.

Abstract: A method for extracting an intracellular peptide, protein or other polypeptide from a whole fermentation broth using a water miscible alcohol, or a water miscible or partially water miscible glycol ether.

Abstract: A process suitable for processing scaled-up amounts of source material in the range of tens of kilograms for the purification of alpha-1 proteinase inhibitor (API) from a mixture of unpurified proteins is provided. More particularly, a process for the purification of API from blood plasma or from plasma fractions to obtain pharmaceutical grade API on a commercial scale is provided. The API produced by the process is highly pure (at least 90% API out of the total protein) and highly active (at least 90% active API). Pharmaceutical compositions comprising the purified API and methods of using same are also described.

Abstract: Combinatorially generated peptides are provided that have binding affinity for polymethylmethacrylate (PMMA). The peptides may be used to deliver benefit agents to various PMMA surfaces.

Abstract: A process for enhancing the recovery yield of proteins, especially plasma proteins, from sources containing the proteins, wherein the sources containing the proteins are frozen at temperatures of ??70° C., and the proteins from a frozen source after thawing are further processed in a per se known manner.

Abstract: The invention provides methods for concentrating a macromolecule from a solution comprising the macromolecule and an organic polymer by first subjecting the solution to ultrafiltration to produce a first retentate solution, then adjusting the conductivity of the first retentate solution such that any protein precipitation induced by the organic polymer is essentially prevented to produce a second retentate solution, and then subjecting the second retentate solution to ultrafiltration. In a preferred embodiment, the conductivity is adjusted by diafiltration against water, suitable diluent or buffer. Preferably, the invention pertains to the concentration of solutions of native or recombinant proteins. The invention further pertains preferably to methods for the concentration of cell culture supernatant comprising a product protein and organic polymers of the PLURONIC family of nonionic block co-polymers, and more preferably comprising PLURONIC F-68 nonionic block co-polymer.

Abstract: The present invention relates to a selectively soluble polymer capable of binding to a desired molecules in an unclarified mixture containing various biological materials and the methods of using such a polymer to purify a molecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and/or salt concentration and is rendered insoluble and precipitates out of solution upon a change in the process conditions. The polymer is capable of binding to the desired molecule (protein, polypeptide, etc) and remains capable of binding to that molecule even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered such as by elution and further processed.

Abstract: The specificity of binding of a zinc finger to a triplet or quadruplet nucleotide target subsite depends upon the location of the zinc finger in a multifinger protein and, hence, upon the location of its target subsite within a larger target sequence. The present disclosure provides zinc finger amino acid sequences for recognition of triplet target subsites having the nucleotide G in the 5?-most position of the subsite, that have been optimized with respect to the location of the subsite within the target site. Accordingly, the disclosure provides finger position-specific amino acid sequences for the recognition of GNN target subsites. This allows the construction of multi-finger zinc finger proteins with improved affinity and specificity for their target sequences, as well as enhanced biological activity.

Abstract: In one aspect, the present invention is directed to isolated soy protein compositions and to the preparation of the isolated soy protein compositions. In another aspect, the present invention is directed to beverage compositions that contain the isolated soy protein compositions and to the preparation of the beverage compositions that contain the isolated soy protein compositions. The beverage is selected from the group consisting of an aqueous acidic liquid or a liquid milk product. The beverage may be prepared and consumed as a cold beverage or a hot beverage or at any temperature of comfort between a cold temperature and a hot temperature. Cold beverages include juices, energy drinks, iced teas, iced coffees, etc. Hot beverages include lattes, mochas, espressos, cappuccinos and teas.

Abstract: The present invention relates to a selectively soluble polymer capable of binding to one or more constituents in a mixture containing various biological materials and the methods of using such a polymer to purify a biomolecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and is rendered insoluble and precipitates out of solution upon a change in the process conditions. While in its solubilized state, the polymer is capable of binding to a selected entity within the stream such as impurities (DNA, RNA, host cell protein, endotoxins, etc) in a cell broth and remains capable of binding to that entity even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered and further processed.

Abstract: The present invention provides a rapid and relatively simple process for purification of acidic proteins expressed in tobacco cells. The process comprises three main purification steps: precipitation with polyethyleneimine, column chromatography with a hydrophobic interaction resin, and column chromatography with hydroxyapatite. The process provides pure or essentially pure protein at a very high yield.

Abstract: A process for removing viruses in fibrinogen solutions and fibrinogen obtained thereof wherein the process starts with an adjusted purified fibrinogen solution, the adjusted purified solution is frozen and then thawed at a temperature between 5 and 20° C., the undissolved materials associated with the fibrinogen are subsequently separated, the temperature is adjusted and the resultant solution is finally subjected to nanofiltration using filters having a pore size smaller than 35 nm.

Abstract: The invention relates to a process for the purification of IL-18 binding protein (IL-18BP) from a fluid using aqueous two-phase partitioning.

Abstract: The present invention relates to a selectively soluble polymer capable of binding to a desired biomolecules in a mixture containing various biological materials and the methods of using such a polymer to purify a biomolecule from such a mixture. The polymer is soluble in the mixture under a certain set of process conditions such as pH or temperature and/or salt concentration and is rendered insoluble and precipitates out of solution upon a change in the process conditions. The polymer is capable of binding to the desired biomolecule (protein, polypeptide, etc) and remains capable of binding to that biomolecule even after the polymer is precipitated out of solution. The precipitate can then be filtered out from the remainder of the stream and the desired biomolecule is recovered such as by elution and further processed.

Abstract: Methods of isolating antibodies by precipitation are disclosed. Various precipitants that can be employed in the invention are also disclosed, with PEG being a preferred precipitant. In a representative embodiment of the invention, the pH of a solution comprising an antibody of interest is adjusted to ±0.5 pH unit of the pI of the antibody, a precipitant such as PEG is added and the antibody of interest is subsequently isolated from the resulting precipitate. The antibody can be further purified if desired or it can be resuspended in a buffer. The invention can be employed as an alternative to or in addition to chromatographic isolation methods, such as methods that employ affinity chromatography.