248 results about "Aggresome" patented technology

Compositions of matter that comprise one or more conformational epitopes found on amyloid peptide aggregates, antibodies to such epitopes and methods for making and using the compositions, eptitopes and / or antibodies. The invention includes synthetic or isolated compositions that contain or consist of certain conformational epitopes that are found on peptide aggregates (e.g., toxic peptide aggregates) present in human or veterinary patients who suffer from, or who are likely to develop, amyloid diseases (e.g., Alzheimer's Disease). The invention includes methods for the detection, treatment and prevention of diseases in humans or animals, using such compositions. The invention further includes antibodies which bind to the conformational epitopes as well as methods for making such antibodies and methods for the detection, treatment and prevention of diseases and / or identification of potential therapies (e.g., drug screening) using such antibodies.

The invention provides methods and compositions for separating impurities during the manufacture of immunoglobulin (Ig) fusion proteins. Examples of impurities which may be removed in accordance with the methods of the invention include inactive forms of the Ig fusion protein and / or aggregates.

The present invention is based, at least in part on the discovery of therapeutic agents capable of preventing, inhibiting or modulating abnormal processing, misfolding or aggregation of protein. The therapeutic agents of the invention may prevent, inhibit or modulate the formation of inclusions. The therapeutic agents of the invention may also be capable of facilitating clearance and / or blocking the cellular toxicity of inclusions to treat or ameliorate disorders characterized by protein aggregation. Compounds which bind to structural motifs commonly found in protein aggregates, such as β-sheets, would represent strong candidates for such compounds and are therefore desirable.

A concentrated, immunoglobulin composition for treating subjects vaccinated against or infected with a pathogenic microorganism, is made by (a) selecting a population of individuals previously vaccinated against antigens associated with the pathogenic microorganism; (b) identifying very high titre individuals by determining the level of specific antibodies immunoreactive with the pathogenic microorganism in the blood of the individuals; (c) combining blood from the very high titre individuals; and (d) purifying and / or concentrating the product of step (c). A concentrated immunoglobulin composition can include specific antibodies immunoreactive with a pathogenic microorganism, wherein the titre of specific antibodies is at least 5 times higher than the average titre of specific antibodies of a population of individuals previously vaccinated against antigens associated with the pathogenic microorganism. The composition has a relatively high protein concentration and a low percentage of protein aggregates. The pathogenic microorganism is preferably smallpox virus or vaccinia virus.

The invention provides methods and compositions for separating impurities during the manufacture of immunoglobulin (Ig) fusion proteins. Examples of impurities which may be removed in accordance with the methods of the invention include inactive forms of the Ig fusion protein and / or aggregates.

The present invention is directed generally to recombinant methods for making a desired pegylated protein and pooling of same. The method(s) yield a polypeptide product containing reduced levels of aggregate thereof pooled to provide the desired pegylated isoforms thereof.

The invention discloses immobilized crosslinked enzyme aggregates (CLEAs) and a preparation method thereof. The crosslinked enzyme aggregates are fixed on a porous microsphere; the preparation method thereof comprises: dispersing detached enzyme needing to be immobilized into the porous microsphere; carrying out depositing and crosslinking on zymoprotein in the porous microsphere in sequence, and finally rinsing the porous microsphere, thus preparing the immobilized crosslinked enzyme aggregates. The method of the immobilized enzyme can be used for immobilizing the enzyme of various types or sources; the immobilized method is simple and easy to be carried out, is easy to be operated, does not need special devices and has low production cost; the prepared crosslinked enzyme aggregates have high stability and strong capacity for resisting trypsinase, has a certain physical form and a stable structure, can be recycled and repeatedly used and can be used for continuous industrial production.

The present invention discloses improved methods of disaggregating protein aggregates, and refolding denatured proteins, using high pressure. In particular, the present invention provides for the use of agitation, high temperature, “stepped” depressurization, dialysis and dilution under pressure to increase the speed and extent of aggregate dissolution and protein refolding.

The present invention provides, among other things, stable formulations for small modular immunopharmaceutical (SMIPTM) proteins. In some embodiments, the present invention provides a formulation containing a lyophilized mixture of a small modular immunopharmaceutical protein, wherein less than 7% of the lyophilized small modular immunopharmaceutical protein exists in aggregated form. Formulations according to the invention may contain buffering agents, stabilizers, bulking agents, surfactants and / or other excipients. The present invention also provides formulations for lyophilization, reconstitution and methods of use thereof.

The present disclosure provides an effective method for the refolding of denatured proteins in solution so that properly folded, biologically active protein in solution is recovered in high yield. The refolding takes place at pressures between about 0.25 kbar to about 3.5 kbar, advantageously at about 1.5 kbar to about 3 kbar. Typically a chaotropic agent is present at a concentration which is not effective for denaturing protein at atmospheric pressure, and optionally, oxidation-reduction reagents can be incorporated in the refolding solution so that native intramolecular disulfide bonds can be formed where that is desired. The method is applicable to substantially all proteins, especially after solubilization and / or denaturation of insoluble protein aggregates, inclusion bodies, or abnormal oligomeric (soluble) aggregates.

The present invention provides a method for subculturing primate embryonic stem cells, and a method for inducing differentiation of the same cell into a vascular endothelial cell and a blood cell. The present invention provides a method comprising culturing primate embryonic stem cells in a medium containing a protein component without using feeder cells and cytokines in a container coated with an extracellular matrix, detaching colonies of the resulting embryonic stem cells in the presence of a cytodetachment agent, and plating the colonies in the similar medium, and a method comprising culturing primate embryonic stem cells in a serum-containing or not containing medium in the presence of cytokine, adhesion-culturing the resulting embryoid body or embroyid body-analogous cellular aggregate in the presence of a cytokine to obtain specific precursor cells, and separating non-adherent cells and adherent cells from the specific precursor cells to obtain blood cells and vascular endothelial precursor cells.

This invention provides a method for purifying a monomeric monoclonal antibody which comprises contacting the sample, wherein the sample comprises the monomeric monoclonal antibody, host cell impurities, dimers, and higher order aggregates, with a Protein A affinity chromatography column; eluting the monomeric monoclonal antibody from the Protein A affinity chromatography column with an elution buffer; and collecting one or more fractions of the monomeric monoclonal antibody to form a Protein A product pool, wherein the product pool comprises less than 5% higher order aggregate, and has a pH from about 3.2 to about 4.5, thereby purifying the monomeric monoclonal antibody from the sample. This invention also provides a method for purifying a monomeric monoclonal antibody which comprises eluting with acetate or citrate, optionally in the presence of amino acids. This invention also provides a method for purifying a monomeric monoclonal antibody which comprises conducting the method within certain temperature ranges.

The present invention relates to a bimodal polymer such as a soluble polymer capable of irreversibly binding to insoluble particulates and a subset of soluble impurities and also capable of reversibly binding to one or more desired biomolecules in an unclarified biological material containing stream and the methods of using such a material to purify one or more desired biomolecules from such a stream without the need for prior clarification. Such a polymer comprises domains of charged pendant groups such as primary, secondary, tertiary or quaternary amines, (first mode) and is rendered insoluble and precipitates out of solution simply upon complexing with oppositely charged solid particulates and a fraction of the soluble impurities in an amount sufficient to form an aggregate that can no longer be held in solution. The polymer further comprises other domains of pendant groups that are charged or uncharged, hydrophilic or hydrophobic or have a ligand that is selective for the biomolecule of interest depending on the process conditions such as pH, ionic strength, salts, and the like (second mode). When present in one mode, such as the uncharged form, said pendant groups are capable of binding to one or more desired biomolecules within the stream (protein, polypeptide, etc) in an unclarified cell broth. The precipitate can then be removed from the stream, such as by being filtered out from the remainder of the stream and the desired biomolecule is recovered such as by selective elution.