Removing Or Inactivating Virus Or Bacterium Or Component Or Product Thereof (e.g., Endotoxin, Etc.) Patents (Class 530/390.1)
-
Patent number: 10519479Abstract: The present invention relates to a cell culture method for adjusting the proportion of G0, G1, G2, and high-mannose galactosylation variants in a population of a recombinant protein produced by a culture of cells in a cell culture medium by supplementing the cell culture medium with manganese at one or more days of the cell culture method duration.Type: GrantFiled: March 13, 2017Date of Patent: December 31, 2019Assignee: ARES TRADING S.A.Inventors: Thomas Solacroup, Matthieu Stettler, Martin Jordan, Hervé Broly
-
Patent number: 10214747Abstract: A new platform method to purify plant-based monoclonal antibodies is provided. Such a method includes an antibody purification platform that involves a standardized procedure for the production of a wide array of different antibodies within a simplified context. The versatility of the overall purification process accords a one-size-fits-all approach for myriad antibody products and includes plant tissue harvesting, extraction and clarification, filtrate generation, a succession of column chromatography procedures, and buffer exposure to provide the desired monoclonal antibodies in proper filtered and purified form for further incorporation and/or use within medicaments and other formulations. Thus, the purified monoclonal antibodies produced thereby such a method are also encompassed within this invention.Type: GrantFiled: October 3, 2014Date of Patent: February 26, 2019Assignee: KENTUCKY BIOPROCESSING, INC.Inventors: Josh Morton, Barry Bratcher, Kelsi Swope, Emmett Ernest Hiatt, III, Steven D. Hume, Larry Zeitlin
-
Patent number: 9557325Abstract: The binding specificity of at least one protein suspended or dissolved in a liquid medium is reversibly altered by exposing the protein to an oxidizing agent or an electric current. A masked protein such as an autoantibody can be detected, isolated and recovered from a biological fluid by subjecting the biological fluid to an oxidizing agent or an electric current to change the binding specificity of masked proteins contained therein.Type: GrantFiled: April 19, 2005Date of Patent: January 31, 2017Assignee: REDOX-REACTIVE REAGENTS LLCInventor: John A. McIntyre
-
Publication number: 20140323695Abstract: A method for manufacturing an antibody formulation in which DNA contaminants are removed by binding the antibody to a protein-A or probtin-G affinity column and eluting the antibody with an acidic eluting solution, preferably of low conductivity.Type: ApplicationFiled: July 11, 2014Publication date: October 30, 2014Inventors: Kozo TAKEDA, Norimichi Ochi, Kimie Ishii, Manabu Matsuhashi, Akinori Imamura
-
Patent number: 8822643Abstract: The present invention provides a process for purifying FV starting from human plasma or a fractionation intermediate thereof, that is simple, scalable to the industrial level and relatively inexpensive compared to the methods described in the literature to date. The invention consists of the use of two anion exchange chromatography steps, the first of which has the purpose of separating the FV from the PTC component factors, while the second has the purpose of isolating the protein of interest from the majority of plasma proteins by means of selective interaction with the weak anion exchange support used. The process developed has also had a viral inactivation step and a viral removal step included, contributing to the safety of the final product obtained, without however significantly altering the process total recovery of FV, and without necessitating the introduction of additional steps for eliminating the inactivating agents used, thanks to the order in which the various steps are conducted.Type: GrantFiled: April 20, 2012Date of Patent: September 2, 2014Assignee: Kedrion S.p.A.Inventors: Paola Rossi, Ilaria Nardini, Pierangelo Giovacchini, Filippo Mori, Claudio Farina
-
Publication number: 20140187755Abstract: The invention relates to a polypeptide comprising: (a) a HC-domain or fragment thereof of the neurotoxic component of a clostridial toxin; and (b) a first LC domain or fragment thereof of the neurotoxic component of a clostridial toxin; and (c) at least one further LC domain or fragment thereof of the neurotoxic component of a clostridial toxin wherein the first and the at least one further LC domain may be the same or different from each other, and wherein each of said fragments of said first and of said at least one further LC domain still exhibits proteolytic activity.Type: ApplicationFiled: February 24, 2014Publication date: July 3, 2014Applicant: MERZ PHARMA GmbH & CO. KGaAInventor: Jurgen FREVERT
-
Publication number: 20130267690Abstract: Methods, compositions and kits for chromatography purification of antibodies are provided. In some embodiments, antibodies are purified by hydroxyapatite (HT) or fluorapatite (FT) that is treated with a polycationic agent. In some embodiments, the antibodies are treated with a polycationic agent that is also a virucidal agent prior to purification.Type: ApplicationFiled: September 18, 2012Publication date: October 10, 2013Applicant: Bio-Rad Laboratories, Inc.Inventor: Peter S. Gagnon
-
Patent number: 8350013Abstract: 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 arginine, and collecting the product using an elution solution. The invention further relates to a product prepared using a method as described herein.Type: GrantFiled: September 7, 2007Date of Patent: January 8, 2013Assignee: Wyeth LLCInventor: Shujun Sun
-
Patent number: 8231876Abstract: 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.Type: GrantFiled: September 15, 2010Date of Patent: July 31, 2012Assignee: Abbott Biotechnology Ltd.Inventors: Min M. Wan, George Avgerinos, Gregory Zarbis-Papastoitsis
-
Patent number: 8222379Abstract: A method of separating a selected ionic component from a sample, comprises contacting the sample with an ionic adsorbent whose charge density is such that the component is bound selectively in the absence of added ionic component that competitively binds the adsorbent.Type: GrantFiled: September 5, 2003Date of Patent: July 17, 2012Assignee: EMD Millipore CorporationInventor: Robert John Noel
-
Patent number: 8188242Abstract: Methods, kits and apparatuses for chromatography purification of antibodies are provided. In some embodiments, antibodies are purified by mixed mode chromatography that does not comprise hydroxyapatite (HT) or fluorapatite (FT). The mixed mode chromatography step is then followed by a HT/FT chromatography step.Type: GrantFiled: April 7, 2009Date of Patent: May 29, 2012Assignee: Bio-Rad Laboratories, Inc.Inventors: Peter S. Gagnon, Hong Chen, Russ Frost
-
Publication number: 20120123002Abstract: A method is disclosed for purifying an antibody monomer, comprising providing a porous membrane comprising a hydrophobic porous substrate, a hydrophilic molecular chain of a different material from that of the porous substrate, immobilized on the surface of pores of the porous substrate, and a side chain of the molecular chain, containing a nitrogen atom to which one to three alkyl groups each having two or three carbon atoms are bonded; passing an antibody solution containing antibody aggregates of dimers or higher-order multimers through the porous membrane to adsorb the antibody aggregates to the porous membrane; and recovering the purified antibody monomer in the passed solution.Type: ApplicationFiled: June 29, 2010Publication date: May 17, 2012Applicants: ASAHI KASEI MEDICAL CO., LTD., ASAHI KASEI CHEMICALS CORPORATIONInventors: Naoyuki Shinohara, Takashi Ishihara, Hironobu Shorataki, Yoshiro Yokoyama
-
Patent number: 8163886Abstract: 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.Type: GrantFiled: December 20, 2007Date of Patent: April 24, 2012Assignee: EMD Millipore CorporationInventor: Wilson Moya
-
Publication number: 20120053325Abstract: The present invention pertains to improved methods of using dye-ligand affinity chromatography for the isolation of antibodies or proteins comprising an antibody fragment (such as Fc fusion proteins) from a mixture of undesirable contaminants. In particular, the use of an organic polymer such as polyethylene glycol (PEG) in the elution phase of an antibody/dye-ligand chromatography isolation procedure results in improved separation of target antibodies from undesirable contaminants. The methods described herein are particularly useful in separating or removing antibody aggregates, misfolded antibodies, and virus contaminants from target antibodies.Type: ApplicationFiled: March 4, 2010Publication date: March 1, 2012Applicant: Biogen Idec MA Inc.Inventors: Robert S. Gronke, Héctor Zaanoni
-
Publication number: 20120015424Abstract: The present invention pertains to methods of using arginine to inactivate or reduce the infectious titer of enveloped viruses potentially present in biological compositions produced by eukaryotic cells (such as a antibodies or other therapeutic proteins). In some embodiments, inactivation or reduction of viral titers by exposure to arginine is achieved in a neutral (pH ˜7) or near neutral (˜pH 6 to ˜pH 8) environment.Type: ApplicationFiled: November 20, 2009Publication date: January 19, 2012Applicant: Biogen Idec MA Inc.Inventors: Keith Selvitelli, Justin McCue
-
Patent number: 8017740Abstract: 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.Type: GrantFiled: February 19, 2010Date of Patent: September 13, 2011Assignee: Bio-Rad Laboratories, Inc.Inventor: Peter S. Gagnon
-
Patent number: 7939492Abstract: Recombinant fragments of Factor C are disclosed. These proteins and peptides show great potency in recognizing, binding to, neutralizing and removing endotoxin. These molecules can thus be used for anti-microbial, anti-endotoxin, and anti-sepsis therapy. SSCrFCES is a 38 kDa protein representing the LPS-binding domain of Factor C. The ability of SSCrFCES to bind lipid A was analyzed using an ELISA-based assay as well as surface plasmon resonance. Surface plasmon resonance similarly carried out for SSCrFC-sushi-1,2,3-GFP, SSCrFC-sushi-1GFP, and SSCrFC-sushi-3GFP confirmed their superior affinity for endotoxin. The 50% endotoxin-neutralizing concentration of SSCrFCES against 200 EU of endotoxin is 0.069 ?M, suggesting that SSCrFCES is an effective inhibitor of LAL coagulation cascade. Although partially attenuated by human serum, as low as 1 ?M of SSCrFCES inhibits the LPS-induced secretion of hTNF-? and hIL-8 by THP-1 and human pheripheral blood mononuclear cells with a potency more superior than polymyxin B.Type: GrantFiled: October 12, 2007Date of Patent: May 10, 2011Assignee: National University of SingaporeInventors: Jeak L. Ding, BoW Ho, Nguan S. Tan
-
Publication number: 20110097344Abstract: The present invention provides compositions and methods useful in the diagnosis and treatment of autoimmunity-related disorders, including cancers and other disorders involving angiogenesis, as well as non-cancer disorders involving a dysfunction in the immune system. In some embodiments, the invention described a plasma assay. In other embodiments, urine assay. In certain other embodiments, the invention provides therapeutic methods comprising removing toxic autoantibodies from the circulation of a patient, e.g., via plasmapheresis, and subsequently infusing the patient with one or more immunoglobulins or immunoglobulin complexes to restore the immune system of the patient to a baseline status whereby the patient's restored immune system either eliminates the source of the disorder (e.g., in the case of cancers) or no longer causes the disease or disorder (e.g., in the case of autoimmune disorders such as multiple sclerosis, psoriasis, latent autoimmune type 1 diabetes in adults (LADA) and the like).Type: ApplicationFiled: October 22, 2010Publication date: April 28, 2011Applicant: EIGER HEALTH PARTNERS, LLC.Inventors: Oleg DARASHKEVICH, Stuart Juckett
-
Patent number: 7863426Abstract: 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.Type: GrantFiled: April 4, 2007Date of Patent: January 4, 2011Assignee: Abbott Biotechnology Ltd.Inventors: Min Wan, George Avgerinos, Gregory Zarbis-Papastoitsis
-
Patent number: 7834162Abstract: 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.Type: GrantFiled: January 5, 2007Date of Patent: November 16, 2010Assignee: Amgen Inc.Inventor: Joe Xin Hua Zhou
-
Publication number: 20100172918Abstract: The present invention relates to a lysin protein originated from bacteriophage, more precisely a lysin protein comprising the amino acid sequence represented by SEQ. ID. NO: 2 which has no harm to human and animals comprising eukaryotic cells owing to its specificity to bacteria and has broad antibacterial activity, and a pharmaceutical composition for the prevention and treatment of infectious disease caused by bacteria comprising the said lysin protein as an active ingredient.Type: ApplicationFiled: April 14, 2009Publication date: July 8, 2010Applicant: iNtRON Biotechnology, Inc.Inventors: SEONGJUN YOON, YUNJAIE CHOI, JEESOO SON, SOOYOUN JUN, HYOUNGROK PAIK, SANGHYEON KANG
-
Patent number: 7714111Abstract: 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.Type: GrantFiled: September 7, 2007Date of Patent: May 11, 2010Assignee: Wyeth LLCInventors: Shujun Sun, Christopher Gallo
-
Patent number: 7691980Abstract: 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.Type: GrantFiled: January 7, 2008Date of Patent: April 6, 2010Assignee: Bio-Rad Laboratories, Inc.Inventor: Peter S. Gagnon
-
Patent number: 7662930Abstract: 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.Type: GrantFiled: December 6, 2006Date of Patent: February 16, 2010Assignee: AMGEN Inc.Inventor: Joe Xin Hua Zhou
-
Publication number: 20090291428Abstract: The invention encompasses an antibody that binds to and substantially inhibits the activity of at least one poxvirus complement inhibitor. Additionally, the application encompasses methods of detecting a poxvirus complement inhibitor and methods of decreasing the activity of a poxvirus complement inhibitor.Type: ApplicationFiled: May 20, 2009Publication date: November 26, 2009Applicant: The Washington UniversityInventors: John P. Atkinson, M. Kathryn Liszewski, Marilyn K. Leung, Paula Bertram
-
Patent number: 7553938Abstract: 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.Type: GrantFiled: February 25, 2005Date of Patent: June 30, 2009Assignee: Octapharma AGInventors: Andrea Buchacher, Günther Iberer, Jürgen Römisch
-
Patent number: 7476722Abstract: A method is provided for separating a protein from one or more other proteins using hydroxyapatite chromatography in which the protein does not bind to hydroxyapatite but the other protein(s) does. In some embodiments, a second protein affixed to a solid support has been used previously to purify the protein by affinity chromatography, and small amounts of the second protein are introduced in the sample during this process. The protein being purified can comprise at least one constant antibody immunoglobulin domain. The second protein can bind to proteins comprising such a domain.Type: GrantFiled: September 13, 2006Date of Patent: January 13, 2009Assignee: Immunex CorporationInventors: Ganesh Vedantham, Clayton Brooks, III, Joanne M Reeder, Andrew M Goetze
-
Patent number: 7465397Abstract: A process is provided for selectively removing protein aggregates from a protein solution in a normal flow (NFF) filtration process. Preferably, it relates to a process for selectively removing protein aggregates from a protein solution in a normal flow (NFF) filtration process and virus particles from a protein solution in a two-step filtration process. In a first step, a protein solution is filtered through one or more layers of adsorptive depth filters, charged or surface modified microporous membranes or a small bed of chromatography media in a normal flow filtration mode of operation, to produce a protein aggregate free stream. The aggregate free protein stream can then be filtered through one or more ultrafiltration membranes to retain virus particles at a retention level of at least 3 LRV and to allow passage therethrough of an aggregate free and virus free protein solution.Type: GrantFiled: July 19, 2006Date of Patent: December 16, 2008Assignee: Millipore CorporationInventors: Martin Siwak, Hong An, Jason R. Comier, Dana Kinzlmaier
-
Patent number: 7462699Abstract: The present invention provides BoNT/A peptides as well as methods of predicting or determining immunoresistance to botulinum toxin therapy in an individual using BoNT/A peptides.Type: GrantFiled: March 29, 2007Date of Patent: December 9, 2008Assignees: Allergan, Inc., Baylor College of MedicineInventor: M. Zouhair Atassi
-
Patent number: 7452539Abstract: Methods for stabilizing polypeptides, such as anti-HER2 antibodies, which have been exposed to urea.Type: GrantFiled: December 11, 2002Date of Patent: November 18, 2008Assignee: Genentech, Inc.Inventors: Jefferson C. Emery, Paul J. McDonald, Rhona M. O'Leary
-
Publication number: 20080124328Abstract: This invention provides antibodies that specifically bind to and neutralize botulinum neurotoxin type A (BoNT/A) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.Type: ApplicationFiled: January 26, 2006Publication date: May 29, 2008Inventors: James D. Marks, Peter Amersdorfer, Isin Geren, Jianlong Lou, Ali Razai, Maria Consuelos Garcia
-
Patent number: 7368542Abstract: 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.Type: GrantFiled: June 9, 2004Date of Patent: May 6, 2008Assignee: Redox-Reactive Reagents LLCInventor: John A. McIntyre
-
Patent number: 7138120Abstract: 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.Type: GrantFiled: July 10, 2001Date of Patent: November 21, 2006Assignee: Statens Serum InstitutInventors: Inga Laursen, Børge Teisner
-
Patent number: 7125552Abstract: 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.Type: GrantFiled: May 13, 2005Date of Patent: October 24, 2006Assignee: Hemacare CorporationInventors: Joshua Levy, Fred Rothstein, Bahman Shimiaei
-
Patent number: 7118675Abstract: A process is provided for selectively removing protein aggregates from a protein solution in a normal flow (NFF) filtration process. Preferably, it relates to a process for selectively removing protein aggregates from a protein solution in a normal flow (NFF) filtration process and virus particles from a protein solution in a two-step filtration process. In a first step, a protein solution is filtered through one or more layers of adsorptive depth filters, charged or surface modified microporous membranes or a small bed of chromatography media in a normal flow filtration mode of operation, to produce a protein aggregate free stream. The aggregate free protein stream can then be filtered through one or more ultrafiltration membranes to retain virus particles at a retention level of at least 3 LRV and to allow passage therethrough of an aggregate free and virus free protein solution.Type: GrantFiled: February 4, 2003Date of Patent: October 10, 2006Assignee: Millipore CorporationInventors: Martin Siwak, Hong An, Jason R. Cormier, Dana Kinzlmaier
-
Patent number: 7115262Abstract: This invention relates to bispecific fusion proteins effective in viral neutralization. More specifically, such proteins have two different binding domains, an inducing-binding domain and an induced-binding domain, functionally linked by a peptide linker. Such proteins, nucleic acid molecules encoding them, and their production and use in preventing or treating viral infections are provided. One prototypical bispecific fusion protein is sCD4-SCFv(17b), in which a soluble CD4 fragment (containing domains D1 and D2) is fused to a single chain Fv portion of antibody 17b via a linker.Type: GrantFiled: March 16, 2000Date of Patent: October 3, 2006Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Edward A. Berger, Christie M. Del Castillo
-
Patent number: 7041798Abstract: 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.Type: GrantFiled: June 23, 2000Date of Patent: May 9, 2006Assignee: Biotest Pharma GmbHInventors: Norbert Kothe, Dieter Rudnick, Michael Kloft
-
Patent number: 6893639Abstract: 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.Type: GrantFiled: October 19, 2001Date of Patent: May 17, 2005Assignee: Hemacare CorporationInventors: Joshua Levy, Fred Rothstein, Bahman Shimiaei
-
Patent number: 6887483Abstract: A method is provided for identifying, isolating, and producing htrB mutants of gram-negative bacterial pathogens. The method comprises mutating the htrB gene of a gram-negative bacterial pathogen so that there is a lack of a functional HtrB protein, resulting in a mutant that lacks one or more secondary acyl chains and displays substantially reduced toxicity as compared to the wild type strain. Also, the present invention provides methods for using a vaccine formulation containing the htrB mutant, or the endotoxin isolated therefrom, to immunize an individual against infections caused by gram-negative bacterial pathogens by administering a prophylactically effective amount of the vaccine formulation.Type: GrantFiled: December 1, 1995Date of Patent: May 3, 2005Assignees: University of Iowa Research Foundation, The Regents of the University of CaliforniaInventors: Michael A. Apicella, Melvin G. Sunshine, Na-Gyong Lee, Bradford W. Gibson
-
Patent number: 6875848Abstract: 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.Type: GrantFiled: January 17, 2002Date of Patent: April 5, 2005Assignee: Probitas Pharma, S.A.Inventors: Pere Ristol Debart, Francisco Rabaneda Gimenez, Ma Teresa Lopez Hernandez
-
Patent number: 6875432Abstract: 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.Type: GrantFiled: October 4, 2001Date of Patent: April 5, 2005Assignees: Genentech, Inc., Novartis AGInventors: Jun Liu, Steven J. Shire
-
Patent number: 6773599Abstract: An affinity ligand-matrix conjugate comprises the matrix and, conjugated thereto by the group Z, a ligand having general formula (I) wherein on X is N and the other X is N, CCL or CCn; A1 and A2 are each independently O, S or N—R1 and R1 is H, C1-6alkyl, C1-6 hydroxyalkyl, benzyl or &bgr;-phenylethyl; B1 and B2 are each independently an optionally substituted hydrocarbon lingkage containing from 1 to 10 carbon atoms; D1 is H or a primary amino, secondary amino, tertiary amino, quaternary ammonium, imidazole, guanidino or amidino group; and D2 is a secondary amino, tertiary amino, quaternary ammonium, imadazole, guanidino or amidino group; of B2-D2 is —CHCOOH—(CH2)3-4—NH2; AND p is 0 or 1. Such conjugates are useful for the separation, isolation, purification, characterisation, identification or quantification of an endotoxin.Type: GrantFiled: May 13, 2002Date of Patent: August 10, 2004Assignee: Prometic Biosciences Ltd.Inventors: Christopher Robin Lowe, Kim Hilary Lawden
-
Publication number: 20040116676Abstract: A method of nanofiltration is provided, comprising passing a solution through at least one nanofiltration membrane having an average pore size of from about 15 nm to about 25 nm under normal flow conditions, wherein the solution components are sufficiently pure and at a concentration that allows the immunoglobulins to pass through at least one nanofiltration membrane. The solutions can contain, for example, immunoglobulins, Factor VIII, or plasmin/plasminogen.Type: ApplicationFiled: September 25, 2003Publication date: June 17, 2004Inventors: JoAnn Hotta, Marina N. Korneyeva, Wytold Lebing
-
Patent number: 6749831Abstract: Compare core LPS (lacking O-polysaccharide side chains) from Gram-negative bacteria are incorporated into a vaccine typically in liposomes. The complete core of E. coli K 12 is particularly useful. Upon administration to a mammal the vaccine stimulates synthesis of antibodies which are cross-protective against smooth and rough forms of LPS from at least two different Gram-negative bacterial strains having different core structures.Type: GrantFiled: April 25, 2000Date of Patent: June 15, 2004Assignee: Medical Defense Technology, LLCInventors: Elliott Bennett-Guerrero, George Robin Barclay, Ian Raymond Poxton, Thomas James McIntosh, David Scott Snyder
-
Patent number: 6737405Abstract: A stabilized protein preparation is described which contains no antithrombin III and is protected against loss of activity during pasteurization by the addition of stabilizers which comprise one or more saccharides as a mixture with more than 0.5 mol/l of one or more amino acids chosen from the group arginine, lysine, histidine, phenylalanine, tryptophan, tyrosine, aspartic acid and its salts or glutamic acid and its salts. Glycine and/or glutamine can also be additionally added to each of these amino acids. A process for the viral inactivation or viral depletion of a protein preparation of this type which contains the abovementioned stabilizers and is subjected to pasteurization or viral depletion by filtration, centrifugation or treatment with detergents or bactericidal or virucidal agents is also described.Type: GrantFiled: May 7, 2001Date of Patent: May 18, 2004Assignee: Aventis Behring GmbHInventors: Juergen Roemisch, Harald Stauss, Hans-Arnold Stoehr
-
Patent number: 6696060Abstract: Methods are disclosed for sterilizing preparation of monoclonal immunoglobulins to reduce the level of active biological contaminants such as viruses, bacteria, yeasts, molds, mycoplasmas, prions and parasites.Type: GrantFiled: June 14, 2001Date of Patent: February 24, 2004Assignee: Clearant, Inc.Inventors: Teri Grieb, Wilson H. Burgess, William N. Drohan, Ren-Yo Forng, Martin J. MacPhee, David M. Mann, Anna McBain
-
Patent number: 6660267Abstract: Compositions and methods are described for preventing and treating sepsis in humans and animals. Surgical patients, low birth weight infants, and burn and trauma victims can be treated prophylactically. Methods for treating acute infections are provided with advantages over current therapeutic approaches.Type: GrantFiled: September 12, 1994Date of Patent: December 9, 2003Assignee: Promega CorporationInventor: Sean B. Carroll
-
Patent number: 6646108Abstract: 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.Type: GrantFiled: July 9, 1998Date of Patent: November 11, 2003Assignee: Baxter AktiengesellschaftInventors: Heinz Leibl, Regine Tomasits, Josef Mannhalter, Hermann Wolf, Martha Eibl
-
Patent number: 6645724Abstract: The horseshoe crab, Carcinoscorpius rotundicauda Factor C cDNA (CrFC21) has been cloned into a shuttle baculoviral vector and another vector suitable for expression in insect cells. The recombinant baculoviral DNA was then transfected into the insect cells for expression of recombinant Factor C. Recombinant Factor C was found to be immunoreactive and is capable of binding both free and bound/immobilized lipid A. It is enzymatically active when triggered by LPS. The rFC is probably of the two-chain form, being cleaved into the heavy and light chains after activation by Gram negative bacterial endotoxin. As low as 0.01 pg (0.001 ng/ml) of LPS was detectable by the rFC, thus, indicating its potentials as a novel generation of “limulus amoebocyte lysate.Type: GrantFiled: April 7, 1999Date of Patent: November 11, 2003Assignee: National University of SingaporeInventors: Jeak Ling Ding, Bow Ho
-
Patent number: RE44558Abstract: An improved process for the purification of antibodies from human plasma or other sources is disclosed. The process involves suspension of the antibodies at pH 3.8 to 4.5 followed by addition of caprylic acid and a pH shift to pH 5.0 to 5.2. A precipitate of contaminating proteins, lipids and caprylate forms and is removed, while the majority of the antibodies remain in solution. Sodium caprylate is again added to a final concentration of not less than about 15 mM. This solution is incubated for 1 hour at 25° C. to effect viral inactivation. A precipitate (mainly caprylate) is removed and the clear solution is diluted with purified water to reduce ionic strength. Anion exchange chromatography using two different resins is utilized to obtain an exceptionally pure IgG with subclass distribution similar to the starting distribution. The method maximizes yield and produces a gamma globulin with greater than 99% purity. The resin columns used to obtain a high yield of IgG retain IgM and IgA.Type: GrantFiled: July 19, 2012Date of Patent: October 22, 2013Assignee: Bayer HealthCare LLCInventors: Patricia Alred, Scott A. Cook, Wytold R. Lebing, Douglas C. Lee, Hanns-Ingolf Paul, Klaus-Peter Radtke