Abstract: The invention provides a method for producing a host cell protein-(HCP) reduced antibody preparation from a mixture comprising an antibody and at least one HCP, comprising an ion exchange separation step wherein the mixture is subjected to a first ion exchange material, such that the HCP-reduced antibody preparation is obtained.

Abstract: A novel method for selectively removing leaked protein A from antibody purified by means of protein A affinity chromatography is disclosed.

Abstract: Various system and method embodiments of the present invention are directed to separating target molecules from complex solutions by affinity column chromatography using organic-solvent-containing eluants. In one embodiment of the present invention, an eluant containing an organic-solvent is used, at a first pH, to remove non-target solutes and suspended entities from an affinity chromatography column. The pH of the eluant is then changed to a second pH, and the organic-solvent-containing eluant is used to elute target molecules from the affinity column chromatography.

Abstract: The present application provides methods of purifying A? binding proteins having a Fc region, for example, anti-A? antibodies or antibody fusions, by adsorbing the A? binding protein to a Fc binding agent, such as, for example, Protein A or Protein G, followed by a wash with a divalent cation salt buffer to remove impurities and subsequent recovery of the adsorbed A? binding protein. The present application also features methods of eluting the purified A? binding protein as well as the incorporation of the methods within a purification train. Kits comprising components for carrying out the methods and instructions for use are also provided.

Abstract: The present application provides methods of purifying polypeptides having a Fc region, for example, antibodies or antibody fusions, by adsorbing the polypeptides to a Fc binding agent, such as, for example, Protein A or Protein G, followed by a wash with a divalent cation salt buffer to remove impurities and subsequent recovery of the adsorbed polypeptides. The present application also features methods of eluting the purified polypeptide as well as the incorporation of the methods within a purification train. Kits comprising components for carrying out the methods and instructions for use are also provided.

Abstract: Methods for reducing the opalescent appearance of a protein preparation by modifying the ionic strength of the preparation, as well as compositions, e.g., pharmaceutical compositions, of concentrated protein with decreased opalescence are disclosed. Purification methods which monitor and/or reduce the salt concentrations at selected steps are also disclosed.

Abstract: The invention relates to methods for isolating a product and/or reducing turbidity and/or impurities from a load fluid comprising the product and one or more impurities by passing the load fluid through a medium, followed by at least one wash solution comprising an arginine derivative, and collecting the product using an elution solution. The invention further relates to a product prepared using a method as described herein.

Abstract: This invention relates to the use of mixed mode chromatography for purification of at least one intact non-aggregated antibody from a mixture containing intact non-aggregated antibodies and undesirable materials, including fragmented or aggregated antibodies, host cell proteins, DNA, endotoxin, and/or virus. This invention further relates to the integration of such a method into a multi-step procedure with other fractionation methods for purification of antibodies suitable for in vivo applications.

Abstract: The present application concerns concentrated protein formulations with reduced viscosity, which are particularly suitable for subcutaneous administration. The application further concerns a method for reducing the viscosity of concentrated protein formulations.

Abstract: Various embodiments of the present invention are directed to multi-step systems and methods for target-molecule purification that employ column-chromatography-based and/or membrane-filtration-based polishing steps. In one described embodiment of the present invention, a target-protein-containing eluate having a high residual salt concentration is collected from a first chromatography column prepared with an affinity-chromatography resin, loaded onto a second chromatography column prepared with a cation-exchange resin, and eluted from the second cation-exchange column using a buffer in which a time-dependent pH gradient is established. In another described embodiment of the present invention, a partially purified target-protein-containing eluate is collected from a chromatography column and further purified by passing the target-protein-containing eluate through a salt-tolerant anion exchanger.

Abstract: Compositions and methods for the therapy of malignant diseases, such as leukemia and cancer, are disclosed. The compositions comprise one or more of a WT1 polynucleotide, a WT1 polypeptide, an antigen-presenting cell presenting a WT1 polypeptide, an antibody that specifically binds to a WT1 polypeptide; or a T cell that specifically reacts with a WT1 polypeptide. Such compositions may be used, for example, for the prevention and treatment of metastatic diseases.

Abstract: Disclosed are applications of oligosaccharides/oligosaccharide mixtures for the production and stabilization of pharmaceutical compositions, chiefly powders, that contain antibodies or antibody derivatives as pharmaceutical active substance. The production of powders is accomplished through spray drying or freeze drying. Also disclosed are the corresponding antibody-containing powders as well as processes for their production.

Abstract: The invention provides a method for the improved processing efficiency of T cell tumor antigen epitopes using bioinformatic means. The proteolytic sites in the generation of 47 experimentally identified HLA-A2.1-restricted immunodominant tumor antigen epitopes was compared to those of 52 documented HLA-A2.1-restricted immunodominant viral antigen epitopes. The amino acid frequencies in the C-terminal cleavage sites of the tumor antigen epitopes, as well as several positions within the 10 amino acid (aa) flanking regions, were significantly different from those of the viral antigen epitopes. These two groups of epitopes may be cleaved by distinct sets of proteasomes and peptidases or similar enzymes with lower efficiencies for tumor epitopes, targeted activation of the immunoproteasomes and peptidases can be achieved that mediate the cleavage of viral epitopes in order to more effectively generate tumor antigen epitopes thus enhancing antigen-specific tumor immunotherapy.

Abstract: In certain embodiments, this application provides humanized antibodies that bind to the EphB4 protein as well as uses of the antibodies for therapeutic purposes.

Abstract: A method of preparing a purified, virus inactivated and virus safe antibody preparation from a starting solution comprising antibodies and contaminants, the method comprising the steps of: (a) adjusting the pH of the starting solution to about 4.6 to about 4.95 in particular to about 4.8 to about 4.95 to produce an intermediate solution; (b) adding caprylate and/or heptanoate ions to the intermediate solution and maintaining the pH at about 4.6 to about 4.95 in particular pH at about 4.8 to about 4.

Abstract: The present invention is directed to a pharmaceutical composition comprising F(ab?)2 antibody fragments that are preferably free from albumin and of whole antibodies and also substantially free of pyrogens, and an effective amount of a pharmaceutically acceptable carrier. It is also directed to a method for the production of a pharmaceutical composition comprising F(ab?)2 antibody fragments using serum or blood plasma of a mammal that has been previously immunized as a source of antibodies. The serum or blood plasma is digested with an enzyme pepsin, followed by separation and purification until the pharmaceutical composition of F(ab?)2 fragments is free of albumin and complete antibodies, and substantially free of pyrogens.

Abstract: Methods for stabilizing polypeptides, such as anti-HER2 antibodies, which have been exposed to urea.

Abstract: The invention features polymeric biomaterials formed by nucleophilic addition reactions to conjugated unsaturated groups. These biomaterials may be used for medical treatments.

Abstract: The binding specificity of at least one plasma protein suspended or dissolved in a liquid medium is altered by exposing the protein to an oxidizing agent or an electric current sufficient to alter its binding specificity. A masked protein such as an autoantibody can be recovered from blood or blood products or extracts by oxidizing the protein to change its binding specificity.

Abstract: The invention provides a method of treating diabetes in a subject, comprising administering to the diabetic subject an immunotoxin, thereby reducing the subject's T-cell population, and administering to the subject pancreatic islet cells from a donor. The immune tolerance inducing treatment regimen, used optionally with adjunct immunosuppressive agents, prevents pancreatic islet cell rejection while maintaining long term islet cell function following xenogeneic and allogeneic pancreatic islet cell transplantation. Thus, the methods of the present invention provide a means for treating diabetes, wherein the need for exogenous insulin or immunosuppressive agents is decreased or eliminated. Also provided is a method of inhibiting a rejection response of a transplant recipient, comprising administering an immunotoxin during the peritransplant period, thereby transiently reducing the number of T-cell lymphocytes and promoting long-term survival of the transplant.

Abstract: Antibodies to the CNA protein and to other regions from the collagen binding domain, including domain CNA19, are provided, and antibodies produced in this manner have been shown to be cross reactive to both Staphylococcus aureus and Staphylococcus epidermidis bacteria and which can thus be used in the prevention and treatment of infections caused by both of these types of bacteria. In addition, medical instruments can be treated using the antibodies of the invention in order to reduce or eliminate the possibility of their becoming infected or further spreading the infection. In particular, the proteins are advantageous because they are cross-reactive and may thus be administered to patients so as to reduce or prevent severe infection by staphylococcal bacteria of more than one species.

Abstract: The invention concerns a method for preparing human immunoglobulin concentrates for therapeutic use, from plasma or a plasma fraction. The method comprises pre-purification and a single anion-exchange chromatography carried out at alkaline pH, thereby enabling the immunoglobulins to be retained on the chromatographic support and fractionated. The method enables to obtain IgG, IgA and IgM concentrates.

Abstract: The present invention relates to a process for purifying immunoglobulin G from a crude immunoglobulin-containing plasma protein fraction. Said process includes a number of steps of which the anion exchange chromatography and the cation exchange chromatography are preferably connected in series. An acetate buffer having a pH of about 5.0-6.0 and having a molarity of about 5-25 mM is preferably used throughout the purification process. The invention further comprises an immunoglobulin product which is obtainable by this process. The invention also relates to an immunoglobulin product which has a purity of more than 98%, has a content of IgG monomers and dimers of more than 98.5%, has a content of IgA less than 4 mg of IgA/l, and contains less than 0.5% polymers and aggregates. Said product does not comprise detergent, PEG or albumin as a stabilizer. The product is stable, virus-safe, liquid and ready for instant intravenous administration.

Abstract: The method for immune serum globulin purification relates to the purification of immune globulins from blood plasma with a high degree of efficiency and a high rate of recovery. The immune globulin source is Cohn's fraction I+II+III or II+III prepared from plasma or plasma intermediates by precipitation of the paste at pH 6.7 to 6.8 in the presence of 20% ethanol and 80% purified water. A glycine extraction is followed by an anion exchange chromatography column step to achieve a significantly high yield and high purity of the concentrated protein.

Abstract: The invention relates to the fractionation of plasma or serum into at least one albumin fraction and one immunoglobulin fraction by hydrophobic interaction chromatography. The fractionation is carried out using an incremental salt gradient, especially an ammonium sulfate buffer. The invention also relates to preparations obtained by using said method and to their use.

Abstract: The present invention pertains to methods for preventing reovirus recognition in the treatment of cellular proliferative disorders, and particularly ras-mediated cellular proliferative disorders, in mammals. The method comprises suppressing or otherwise inhibiting the immune system of the mammal and, concurrently or subsequently, administering to the proliferating cells an effective amount of one or more reoviruses under conditions which result in substantial lysis of the proliferating cells. The methods may include the selective removal of immune constituents that may interfere with the systemic delivery of the virus; preventing reovirus recognition by the host immune system; and removal of the virus from an immune suppressed or immune incompetent host following treatment with reovirus. Alternatively, reovirus may be administered to a mammal with a diminished immune response system under conditions which result in substantial lysis of the proliferating cells.

Abstract: The method for immune serum globulin purification relates to the purification of immune globulins from blood plasma with a high degree of efficiency and a high rate of recovery. The immune globulin source is Cohn's fraction I+II+III or II+III prepared from plasma or plasma intermediates by precipitation of the paste at pH 5.7 to 5.8 in the presence of 20% ethanol and 80% purified water. A glycine extraction is followed by an anion exchange chromatography column step to achieve a significantly high yield and high purity of the concentrated protein.

Abstract: The gammaglobulin is extracted from a fraction isolated by fractionation with ethanol in the presence of a carbohydrate, and after reducing the content of contaminants with PEG, it is applied to an anionic resin exchange column, an effluent being obtained in which the PEG content is subsequently reduced by ultrafiltration and which is concentrated in order to carry out sequentially an optional treatment at an acid pH and at least one of the following steps of viral inactivation, consisting of pasteurisation and a treatment with solvent/detergent, the product afterwards being precipitated and washed with PEG in order to eliminate any chemical viral inactivation reagents and then, by solubilisation and change of pH, the protein contaminants, and finally purified by ultrafiltration to reduce the volume and the PEG content, then carrying out an optional virus filtration and subsequent concentration.

Abstract: The present application concerns concentrated protein formulations with reduced viscosity, which are particularly suitable for subcutaneous administration. The application further concerns a method for reducing the viscosity of concentrated protein formulations.

Abstract: The invention provides methods for treating or preventing disorders associated with expression of BAFF comprising BAFF and fragments thereof, antibodies, agonists and antagonists.

Abstract: A pharmaceutical composition for treating allergy is described. The composition comprises as an active ingredient a recombinant polyclonal antibody or a mixture of different monoclonal antibodies capable of reacting with or binding to an allergen together with one or more pharmaceutically acceptable excipients. The composition may be used topically as a solution, dispersion, powder, or in the form of microspheres. The polyclonal antibody is preferably a recombinant polyclonal antibody produced by phage display technology. The pairing of specific immunoglobulin variable region light chain and heavy chain maintained from the original polyclonal immune response or selected by panning using the allergen in question is preferably maintained by bulk transfer of the pairs into an expression vector.

Abstract: Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.

Abstract: The present invention is directed to a pharmaceutical composition comprising F(ab′)2 antibody fragments that are preferably free from albumin and of whole antibodies and also substantially free of pyrogens, and an effective amount of a pharmaceutically acceptable carrier. It is also directed to a method for the production of a pharmaceutical composition comprising F(ab′)2 antibody fragments using serum or blood plasma of a mammal that has been previously immunized, as a source of antibodies. The serum or blood plasma is digested with pepsin, followed by separation and purification until the pharmaceutical composition of F(ab′)2 fragments is free of albumin and complete antibodies, and substantially free of pyrogens.

Abstract: Method of reducing the anticomplement activity (ACA) resulting from viral inactivation treatment of a solution of antibodies, the method comprising contacting the solution with a trialkylphosphate, such as tri-n-butyl phosphate, and a detergent, such as sodium cholate, under conditions sufficient to reduce substantially the virus activity, and then incubating the solution under controlled conditions of time, pH, temperature, and ionic strength such that the anticomplement activity is reduced to an acceptable level. In a preferred embodiment, the ACA is reduced to less than 60 CH50 units/mL, the incubation is for at least about ten days at a pH from 3.5 to 5.0, the temperature is maintained within a range of 2 to 50° C., and the ionic strength of the solution is less than about 0.001 M.

Abstract: A method for the separation of IgG and IgA from an immunoglobulin-containing starting material is described, whereby the method is characterized in that (i) IgG and optionally IgA are adsorbed to a solid inorganic carrier material, (ii) IgA is isolated from the eluate, optionally after selective desorption, whereas IgG remains on the carrier material, and optionally (iii) IgG is isolated from the adsorbate. Furthermore, an IgA preparation is disclosed which demonstrates a low tendency to form aggregates.

Abstract: The present invention pertains to methods for preventing reovirus recognition in the treatment of cellular proliferative disorders, and particularly ras-mediated cellular proliferative disorders, in mammals. The method comprises suppressing or otherwise inhibiting the immune system of the mammal and, concurrently or subsequently, administering to the proliferating cells an effective amount of one or more reoviruses under conditions which result in substantial lysis of the proliferating cells. The methods may include the selective removal of immune constituents that may interfere with the systemic delivery of the virus; preventing reovirus recognition by the host immune system; and removal of the virus from an immune suppressed or immune incompetent host following treatment with reovirus. Alternatively, reovirus may be administered to a mammal with a diminished immune response system under conditions which result in substantial lysis of the proliferating cells.

Abstract: There is provided the use of a low molecular weight thrombin inhibitor for the manufacture of a medicament for the treatment by dialysis, particularly haemodialysis, of a patient in need of such treatment, in which the thrombin inhibitor is provided in the dialysing solution, as well as dialysing solutions and concentrates including low molecular weight thrombin inhibitors, such as melagatran.

Abstract: Liquid compositions for intravenous administration that comprise an aqueous solution of immunoglobulin and methods of preparing such compositions are disclosed. The solution has a pH in the range of 5.0 to 5.8 and an ionic strength is the range 0.02 to 0.25. The liquid compositions are formulated so as to be stable upon storage such that the immunoglobulin does not substantially aggregate nor degrade and maintains acceptable levels of anti-complementary activity, PKA activity and kallikrein activity during storage for an extended period at a temperature in the range of 4° C. to 25° C.

Abstract: A method for producing an immunoglobulin preparation for intravenous injection, which comprises the steps of: fractionating an immunoglobulin-containing solution with 4 to 10 w/v% of polyethylene glycol having a molecular weight of from 1,000 to 10,000, at a pH value of from 4.5 to 6.5, an ionic strength of from 0.0001 to 0.1 M and a temperature of from 0 to 4° C. to recover a supernatant fraction; and concentrating the supernatant fraction at a pH of from 3.5 to 5.0.

Abstract: The present invention relates to a process for purifying immunoglobulin G from a crude immunoglobulin-containing plasma protein fraction. Said process includes a number of steps of which the anion exchange chromatography and the cation exchange chromatography are preferably connected in series. An acetate buffer having a pH of about 5.0-6.0 and having a molarity of about 5-25 mM is preferably used throughout the purification process. The invention further comprises an immunoglobulin product which is obtainable by this process. The invention also relates to an immunoglobulin product which has a purity of more than 98%, has a content of IgG monomers and dimers of more than 98.5%, has a content of IgA less than 4 mg of IgA/l, and contains less than 0.5% polymers and aggregates. Said product does not comprise detergent, PEG or albumin as a stabilizer. The product is stable, virus-safe, liquid and ready for instant intravenous administration.

Abstract: Concentrated monoclonal antibody preparations for administration to humans are described in which the antibody is present at a concentration of greater than 100 mg/ml and as high as 350 mg/ml.

Abstract: An aqueous protein solution buffered with a potassium phosphate buffer, in which the ratio of potassium ions to sodium ions in the solution is at least 10:1, is resistant to the formation of protein aggregates and particles under conditions of freezing, thawing, lyophilization, and reconstitution.