Removing, Dissociating, Or Preventing The Formation Of Aggregated, Denatured, Fragmented, Or Polymerized Immunoglobulin Or Antibody; Or Preventing Or Reducing Complement Fixation Or Binding; Or Reducing Antigenicity; Or Removing, Inactivating, Or Inhibiting Contaminating Plasma Proteins (e.g., Proteolytic Enzymes, Etc.) Patents (Class 530/390.5)
  • Patent number: 10076749
    Abstract: The present invention provides novel methods of cell disruption and release of biomolecules from a cell. The invention comprises the use of positively and/or negatively charged microparticles comprising ground resin. It is particularly useful for purification of biomolecules from cell culture.
    Type: Grant
    Filed: August 25, 2014
    Date of Patent: September 18, 2018
    Assignees: BOEHRINGER INGELHEIM RCV GMBH & CO KG, SANDOZ AG
    Inventors: Rainer Hahn, Alois Jungbauer, Alexandru Trefilov
  • Patent number: 10023608
    Abstract: Disclosed are methods of purifying a protein sample. More specifically, provide are methods of removing or reducing the amount of high molecular weight species and/or high mannose species from a protein sample using a mixed mode chromatography step and a hydrophobic interaction chromatography step.
    Type: Grant
    Filed: March 13, 2014
    Date of Patent: July 17, 2018
    Assignee: AMGEN INC.
    Inventors: Junfen Ma, Xiaoyang Zhao, Brian Williamson
  • Patent number: 9896501
    Abstract: The present invention provides, among other aspects, methods for the manufacture of plasma-derived immunoglobulin G compositions highly enriched for anti-brain disease related protein antibodies (e.g., anti-A?, anti-RAGE, and anti-?-synuclein antibodies). Advantageously, the methods provided do not affect the manufacturing processes or capabilities for producing plasma-derived IgG therapeutics. Plasma-derived IgG compositions that are highly enriched for anti-brain disease related protein antibodies (e.g., anti-A?, anti-RAGE, and anti-?-synuclein antibodies), as also provided here. Methods for the treatment of brain diseases and disorders by administration of plasma-derived IgG compositions highly enriched for anti-brain disease related protein antibodies (e.g., anti-A?, anti-RAGE, and anti-?-synuclein antibodies), are also provided.
    Type: Grant
    Filed: March 14, 2014
    Date of Patent: February 20, 2018
    Assignees: Baxalta Incorporated, Baxalta GmbH
    Inventors: Lucia Gnauer, Harald Arno Butterweck, Theresa Bauer, Alfred Weber, Wolfgang Teschner, Hans-Peter Schwarz
  • Patent number: 9631008
    Abstract: The current invention reports a method for purifying an immunoglobulin, wherein the method comprises applying an aqueous, buffered solution comprising an immunoglobulin in monomeric, in aggregated, and in fragmented form to an anion exchange chromatography material under conditions whereby the immunoglobulin in monomeric form does not bind to the anion exchange material, and recovering the immunoglobulin in monomeric form in the flow-through from the anion exchange chromatography material, whereby the buffered aqueous solution has a pH value of from 8.0 to 8.5. In one embodiment the anion exchange chromatography material is a membrane anion exchange chromatography material.
    Type: Grant
    Filed: December 18, 2009
    Date of Patent: April 25, 2017
    Assignee: Hoffmann-La Roche Inc.
    Inventors: Marc Pompiati, Andreas Schaubmar
  • Patent number: 9408568
    Abstract: A biological fluid sampling device adapted to receive a blood sample and includes a housing having a reservoir disposed therein and a first cavity in fluid communication with the reservoir is disclosed. The biological fluid sampling device includes a first test element removably receivable within the first cavity and a lancet having a puncturing element. Additionally, the housing may include a second cavity in fluid communication with the reservoir and a second test element removably receivable within the second cavity. With the blood sample received within the reservoir of the biological fluid sampling device, the first test element and the second test element are adapted to receive a portion of the blood sample. In this manner, the biological fluid sampling device allows for a blood sample to be collected on a plurality of test elements simultaneously. In one embodiment, the biological fluid sampling device contains a sample stabilizer.
    Type: Grant
    Filed: April 14, 2014
    Date of Patent: August 9, 2016
    Assignee: Becton, Dickinson and Company
    Inventors: Gary D. Fletcher, Bradley M. Wilkinson
  • Patent number: 9380972
    Abstract: A blood collection device adapted to receive a multi-component blood sample is disclosed. After collecting the blood sample, the blood collection device separates a plasma portion from a cellular portion. After separation, the blood collection device is able to transfer the plasma portion of the blood sample to a point-of-care testing device. The blood collection device of the present disclosure also provides a closed collection and transfer system that reduces the exposure of a blood sample and provides fast mixing of a blood sample with a sample stabilizer. The blood collection device is engageable with a blood testing device for closed transfer of a portion of the plasma portion from the blood collection device to the blood testing device. The blood testing device is adapted to receive the plasma portion to analyze the blood sample and obtain test results.
    Type: Grant
    Filed: April 14, 2014
    Date of Patent: July 5, 2016
    Assignee: Becton, Dickinson and Company
    Inventors: Gary D. Fletcher, Ashley Rachel Rothenberg, Craig A. Gelfand, Daniel J. Marchiarullo, Bradley M. Wilkinson
  • Patent number: 9193760
    Abstract: The invention provides methods and materials for using apatite chromatography supports to dissociate and remove contaminants that are complexed to biological products. The invention further provides materials and methods for dissociating aggregations of target biological molecules or improperly folded target molecules to improve purification of the target molecule.
    Type: Grant
    Filed: September 20, 2011
    Date of Patent: November 24, 2015
    Assignee: Bio-Rad Laboratories, Inc.
    Inventor: Peter S. Gagnon
  • Patent number: 9096648
    Abstract: The present invention provides novel and improved protein purification processes which incorporate certain types of carbonaceous materials and result in effective and selective removal of certain undesirable impurities without adversely effecting the yield of the desired protein product.
    Type: Grant
    Filed: August 2, 2012
    Date of Patent: August 4, 2015
    Assignee: EMD Millipore Corporation
    Inventors: Nanying Bian, Christopher Gillespie, Matthew T. Stone, Mikhail Kozlov, Jie Chen, Martin Siwak
  • Publication number: 20150148526
    Abstract: Methods for reduction of aggregate levels in antibody and other protein preparations through treatment with low concentrations of electropositive organic additives (e.g., ethacridine, chlorhexidine, or polyethylenimine) in combination with ureides (e.g., urea, uric acid, or allantoin) or organic modulators (e.g., nonionic organic polymers, surfactants, organic solvent or ureides). Some aspects of the invention relate to methods for reducing the level of aggregates in conjunction with clarification of cell culture harvest. It further relates to the integration of these capabilities with other purification methods to achieve the desired level of final purification.
    Type: Application
    Filed: November 26, 2014
    Publication date: May 28, 2015
    Inventor: Peter Gagnon
  • Patent number: 8926973
    Abstract: Disclosed are compositions and methods for producing fusion proteins with reduced immunogenicity. Fusion proteins of the invention include a junction region having an amino acid change that reduces the ability of a junctional epitope to bind to MHC Class II, thereby reducing its interaction with a T-cell receptor. Methods of the invention involve analyzing, changing, or modifying one or more amino acids in the junction region of a fusion protein in order to identify a T-cell epitope and reduce its ability to interact with a T cell receptor. Compositions and methods of the invention are useful in therapy.
    Type: Grant
    Filed: May 26, 2011
    Date of Patent: January 6, 2015
    Assignee: Merck Patent GmbH
    Inventors: Stephen D. Gillies, Jeffrey Way, Anita A. Hamilton
  • Publication number: 20140371431
    Abstract: A process for synthesizing and separating secretory IgA from a mixture of IgA monomer and IgA dimer is provided. The process includes covalently binding affinity tagged or epitope tagged recombinant secretory component to the IgA dimer in the mixture and binding the affinity tagged or an epitope tagged secretory IgA to immobilized moieties on the solid phase support resin to which the affinity tag or epitope tag binds and then eluting the affinity tagged or an epitope tagged secretory IgA with release buffer. A process for synthesizing and separating secretory IgM from a mixture of IgM and other plasma proteins is also provided. The process includes covalently binding affinity tagged or an epitope tagged recombinant secretory component to the IgM in the mixture and binding the affinity tagged or an epitope tagged secretory IgM to immobilized moieties on the solid phase support resin and then eluting the peptide tagged secretory IgM with a release buffer.
    Type: Application
    Filed: September 3, 2014
    Publication date: December 18, 2014
    Inventors: Stephen C. Brown, Michael R. Simon, Blaise Corthésy
  • Publication number: 20140243210
    Abstract: An immunoglobulin binding peptide having the general formula, from amino terminus to carboxy terminus, of Z—R1—R2—R3—R4—R5—R6—X, is described, wherein: R1 is H or Y; R2 is a hydrophobic, preferentially aromatic, amino acid (for example W, F, Y, V); R3 is a positively charged or aromatic amino acid (for example R, H, F, W); R4 is a hydrophobic or positively charged amino acid (for example G, Y, R, K, L); R5 is a positively charged or aromatic amino acid (for example W, F, R, H, Y); R6 a random amino acid but preferably hydrophobic or negatively charged (for example V, W, L, D, H); X is present or absent and when present is a linking group; and Z is present or absent and when present is a capping group bonded to the N terminus of R1; and wherein the amino acids of said peptide are in D form, L form, or a combination thereof.
    Type: Application
    Filed: May 2, 2012
    Publication date: August 28, 2014
    Inventors: Ruben Carbonell, Haiou Yang, Patrick Gurgel
  • Publication number: 20140213774
    Abstract: Suggested is a process for obtaining immunoglobulins, wherein (a) colostral milk from days 0 to 7 is subjected to thermal treatment, skimming the cream, (b) the skimmed milk such obtained is subjected to sterile microfiltration thus producing a first retentate R1 which contains the casein, and a first permeate P1, (c) the first permeate P1 is subjected to ultrafiltration thus producing a second permeate P2 which contains lactose and minerals, and a second retentate R2, in which the immunoglobulins are concentrated.
    Type: Application
    Filed: January 30, 2014
    Publication date: July 31, 2014
    Applicant: DMK Deutsches Milchkontor GmbH
    Inventor: Sven-Rainer Doring
  • Patent number: 8778349
    Abstract: The intrinsically disordered sequences—or “intrinsically disorded sequences” or IDSeq—proteins should be flexible to ensure a controlled interaction between proteins. In the development of the diseases, IDSeq are modified and polymerized. The invention describes the method of preparation of the drugs against cancers, the degenerative diseases and the infectious illness, by the induction of an immune reaction against IDSeq modified in a covalent way (IDSeqC) and polymerized (pIDSeqC), and leading to a new network of protein signaling, named here “misfoldome”, causing the diseases. The invention describes the preparation of vaccines by the use of polymers of IDSeqC. Peptides of the pIDSeqC are prepared in vitro, and introduced into a living organism to induce an immunological response, which eliminates the “misfoldome” and cures the diseases. The method is employed for the preparation of active or passive vaccines.
    Type: Grant
    Filed: October 30, 2008
    Date of Patent: July 15, 2014
    Inventor: Halina Malina
  • Patent number: 8754195
    Abstract: The present invention relates to formulations comprising sucrose, and methods of making such formulations, wherein the sucrose content promotes the reduction or elimination of the reversible self-association (RSA) tendency of the antibody in the formulation. The present invention also relates to formulations comprising an anti-PDGFR-alpha antibody or antibody fragment. Such antibodies can be used in various methods of treatment. The application further relates to a method of eliminating or reducing the RSA tendency of antibodies in a formulation.
    Type: Grant
    Filed: July 1, 2011
    Date of Patent: June 17, 2014
    Assignee: MedImmune, LLC
    Inventors: Mariana N. Dimitrova, Neil Mody
  • Publication number: 20140154270
    Abstract: The present invention is directed to methods for purifying a non-human antibody, or antigen binding portion thereof, exhibiting weak binding strength and low binding capacity for Protein A chromatography media. In one aspect, a kosmotropic salt solution is employed to promote the hydrophobic interaction between the non-human antibody, or antigen binding portion thereof, and the Protein A ligand, thereby enhancing the binding of the non-human antibody, or antigen binding portion thereof, to the Protein A chromatography media. In another aspect, the concentration of the non-human antibody, or antigen binding portion thereof, in a sample comprising the antibody, or antigen binding portion thereof, exposed to a Protein A chromatography media is increased to enhance the binding of the non-human antibody, or antigen binding portion thereof, on the Protein A chromatography media.
    Type: Application
    Filed: November 20, 2013
    Publication date: June 5, 2014
    Inventors: Chen Wang, Susan E. Lacy, Randolph Huelsman
  • Publication number: 20140141021
    Abstract: The present invention relates to a method for preparing a concentrate of polyvalent immunoglobulins with view to therapeutic use, from an initial solution of blood plasma or a plasma fraction enriched with immunoglobulins, comprising the steps for removing the protein contaminants by precipitation with caprylic acid in order to obtain a solution free of proteases, and for separating by chromatography on a fluidized bed the solution free of proteases, said method allowing a concentrate of human polyvalent immunoglobulins with a yield of more than 4.5 g of immunoglobulins per liter of blood plasma applied to be obtained.
    Type: Application
    Filed: July 11, 2012
    Publication date: May 22, 2014
    Applicant: LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES
    Inventors: Abdessatar Chtourou, Damien Bataille, Georges Michaux
  • Publication number: 20140128575
    Abstract: The invention concerns methods and means for preventing the reduction of disulfide bonds during the recombinant production of disulfide-containing polypeptides. In particular, the invention concerns the prevention of disulfide bond reduction during harvesting of disulfide-containing polypeptides, including antibodies, from recombinant host cell cultures.
    Type: Application
    Filed: October 1, 2013
    Publication date: May 8, 2014
    Applicant: Genentech, Inc.
    Inventors: Yung-Hsiang KAO, Michael W. LAIRD, Melody Trexler SCHMIDT, Rita L. WONG, Daniel P. HEWITT
  • Publication number: 20140072585
    Abstract: Disclosed herein are compositions and methods for purifying antibody products from a sample matrix. In particular, the present invention relates to compositions and methods for purifying antibody products employing hydrophobic interaction chromatography media. In certain embodiments, the invention provides a method for reducing process-related impurities (e.g., host cell proteins), as well as product-related substances, including molecular weight variants (e.g., aggregates and fragments of the antibody product).
    Type: Application
    Filed: March 14, 2013
    Publication date: March 13, 2014
    Applicant: ABBVIE INC.
    Inventor: ABBVIE INC.
  • Publication number: 20140051839
    Abstract: A process for reduction and/or removal of FXI and FXIa from a source solution containing said coagulation factors and as main components immunoglobulins comprising the following steps: a) contacting the FXI and/or FXIa containing solution with an affinity chromatographic gel wherein heparin or heparan is linked to the matrix material; b) allowing adsorption of FXI and/or FXIa and c) separation of the liquid deprived of FXI and/or FXIa from the adsorption media.
    Type: Application
    Filed: November 16, 2011
    Publication date: February 20, 2014
    Applicant: Octapharma AG
    Inventors: Petra Schultz, Gerhard Gruber, Frederic Bal, Frank Marks, Stefan Winge
  • Publication number: 20140044742
    Abstract: The invention concerns a method for preparing a plasma product depleted of one or more thrombogenic factors, comprising the combination of at least two steps chosen from among an ethanol fractionation step, a filtration-adsorption step, a precipitation step with caprylic acid and a chromatography step on ion exchange resin.
    Type: Application
    Filed: April 19, 2012
    Publication date: February 13, 2014
    Applicant: LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES
    Inventors: Monique Ollivier, Philippe Paolantonacci
  • Publication number: 20130317200
    Abstract: The invention provides methods of purifying antibodies using various antibody-specific purification media to rapidly and efficiently separate mixtures of antibodies, antibody fragments and/or antibody components to isolate a desired antibody product from the mixture. The invention relates to the purification of bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule, e.g., antibodies composed of a single heavy chain and two different light chains, one containing a Kappa constant domain and the other a Lambda constant domain, including antibodies of different specificities that share a common heavy chain. The invention also provides the methods of efficiently purifying intact antibodies by separating the intact antibody from non-intact antibodies including free light chains.
    Type: Application
    Filed: October 19, 2012
    Publication date: November 28, 2013
    Applicant: Novlmmune S.A.
    Inventors: Greg Elson, Nicolas Fouque, Jean-Francois Depoisier, Nicolas Fischer, Giovanni Magistrelli
  • Patent number: 8569464
    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.
    Type: Grant
    Filed: December 16, 2008
    Date of Patent: October 29, 2013
    Assignee: EMD Millipore Corporation
    Inventors: Wilson Moya, Jad Jaber
  • Publication number: 20130237692
    Abstract: Anion exchange-hydrophobic mixed mode ligands and methods of their use are provided.
    Type: Application
    Filed: March 5, 2013
    Publication date: September 12, 2013
    Applicant: Bio-Rad Laboratories, Inc.
    Inventors: Jiali Liao, Russell Frost
  • Publication number: 20130197198
    Abstract: This invention relates to the application of hydroxyapatite chromatography to the purification of at least one antibody from a preparation containing high molecular weight aggregates. Further, this invention relates to an integration of ceramic hydroxyapatite chromatography into a combination chromatographic protocol for the removal of high molecular weight aggregates from an antibody preparation.
    Type: Application
    Filed: March 14, 2013
    Publication date: August 1, 2013
    Applicant: WYETH LLC
    Inventor: WYETH LLC
  • Publication number: 20130131323
    Abstract: The invention relates to a system and method for the stable storage of sensitive biological or chemical target substance, in a bound form on certain capture media. The method comprised providing a sample containing the target substance in a suitable buffer; combining the sample with a capture media to effect reversible binding of the target substance to the capture media; and storing the capture media with the target substance at between about ?20 and 20° C.; and recovering the target substance from the capture media. The target substance recovered maintains the desired activity. Also provides are methods for reducing aggregates in the sensitive biological or chemical target substance.
    Type: Application
    Filed: April 28, 2011
    Publication date: May 23, 2013
    Applicant: GE HEALTHCARE BIO-SCIENCES AB
    Inventors: James Van Alstine, Johan Ohman, Philippe Busson, Ronnie Palmgren, Klas Allmer, John Daicic
  • Patent number: 8440799
    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.
    Type: Grant
    Filed: October 12, 2010
    Date of Patent: May 14, 2013
    Assignees: Janssen Alzheimer Immunotherapy, Wyeth LLC
    Inventors: Ranganathan Godavarti, Timothy Iskra
  • Patent number: 8398984
    Abstract: The present invention is to provide a removal promoter for apoptotic cells which is capable of immediately removing apoptotic cells in vivo by macrophages, or a removal inhibitor which inhibits the removal of apoptotic cells in vivo by macrophages. A removal promoter for apoptotic cells in vivo containing the milk fat globule-EGF factor 8-L (MFG-E8-L), MFG-E8-L mutant having removal promotion action for apoptotic cells in vivo by macrophages, or preferably a recombinant human or mouse MFG-E8-L, or a recombinant human or mouse MFG-E8-L mutant as an active ingredient is prepared. Such removal promoters specifically bind to apoptotic cells and promote the phagocytosis of apoptotic cells by macrophages by recognizing aminophospholipids such as phosphatidylserine exposed on apoptotic cell surface. On the other hand, a point mutation (D89E) MFG-E8-L mutant is used as a removal inhibitor.
    Type: Grant
    Filed: September 30, 2009
    Date of Patent: March 19, 2013
    Assignee: Japan Science and Technology Agency
    Inventor: Shigekazu Nagata
  • Patent number: 8394933
    Abstract: It is an object of the present invention to provide: a protein refolding column filler, which is effective for the refolding, namely, the activation of the function, of an inactive protein with an as yet unformed higher order structure produced in Escherichia coli or the like, or a protein whose conformation has been changed due to a certain cause and which has become inactivated; and a column filled with the aforementioned column filler. The present invention provides a protein refolding column filler, which comprises zeolite with BEA structure (Zeolite Beta) that is granulated into a particle state.
    Type: Grant
    Filed: April 4, 2008
    Date of Patent: March 12, 2013
    Assignee: FUJIFILM Corporation
    Inventors: Masayuki Kawakami, Tatsuo Tsunoda, Hideaki Togashi, Takayuki Nara, Shun-ichi Matsuura, Chisato Sekikawa, Akiko Kawai, Akiyoshi Kawata, Fujio Mizukami, Kengo Sakaguchi
  • Publication number: 20130052209
    Abstract: Compositions and methods that include stabilized protein drugs are described. In addition, protein drug formulations that are more stable under ambient conditions are described. The formulations include one or more polyamino acid ligands of the protein drug.
    Type: Application
    Filed: April 22, 2011
    Publication date: February 28, 2013
    Applicant: PURDUE RESEARCH FOUNDATION
    Inventors: Elizabeth Murphy Topp, Frederick E. Regnier, Jun Zhang
  • Patent number: 8362217
    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.
    Type: Grant
    Filed: December 20, 2007
    Date of Patent: January 29, 2013
    Assignee: EMD Millipore Corporation
    Inventors: Wilson Moya, Jad Jaber
  • Publication number: 20130022625
    Abstract: An objective of the present invention is to provide stable antibody-containing formulations which are suitable for subcutaneous administration and in which aggregation formation is suppressed during long-term storage. The present inventors discovered that a significant stabilization effect was achieved by using an acidic amino acid, aspartic acid or glutamic acid as a counter ion species in histidine buffer or tris(hydroxymethyl)aminomethane, specifically by using histidine-aspartate buffer or histidine-glutamate buffer, or tris(hydroxymethyl)aminomethane-aspartate or tris(hydroxymethyl)aminomethane-glutamate as a buffer. The present inventors also discovered that a significant stabilization effect was achieved by using an acidic amino acid, aspartic acid or glutamic acid, as a counter ion species to a basic amino acid such as arginine, specifically by using arginine-aspartate or arginine-glutamate.
    Type: Application
    Filed: January 20, 2011
    Publication date: January 24, 2013
    Applicant: Chugai Seiyaku Kabushiki Kaisha
    Inventors: Tomoyuki Igawa, Chifumi Moriyama
  • Patent number: 8350013
    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 arginine, and collecting the product using an elution solution. The invention further relates to a product prepared using a method as described herein.
    Type: Grant
    Filed: September 7, 2007
    Date of Patent: January 8, 2013
    Assignee: Wyeth LLC
    Inventor: Shujun Sun
  • Patent number: 8231876
    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.
    Type: Grant
    Filed: September 15, 2010
    Date of Patent: July 31, 2012
    Assignee: Abbott Biotechnology Ltd.
    Inventors: Min M. Wan, George Avgerinos, Gregory Zarbis-Papastoitsis
  • Publication number: 20120142901
    Abstract: The present invention provides a method of purifying an antibody by protein A affinity chromatography. More specifically, the present invention provides a technique relating to an elution buffer solution which provides a good antibody recovery rate without denaturation.
    Type: Application
    Filed: November 29, 2011
    Publication date: June 7, 2012
    Inventors: Ryosuke Yumioka, Daisuke Ejima, Tsutomu Arakawa
  • Patent number: 8188242
    Abstract: 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: Grant
    Filed: April 7, 2009
    Date of Patent: May 29, 2012
    Assignee: Bio-Rad Laboratories, Inc.
    Inventors: Peter S. Gagnon, Hong Chen, Russ Frost
  • Patent number: 8163886
    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.
    Type: Grant
    Filed: December 20, 2007
    Date of Patent: April 24, 2012
    Assignee: EMD Millipore Corporation
    Inventor: Wilson Moya
  • Publication number: 20120093839
    Abstract: In a broad aspect the present invention generally relates to novel dimer-complexes (herein called “non-fused-dimers” or NFDs) comprising single variable domains, methods of making these complexes and uses thereof. These non-covalently bound dimer-complexes consist of two identical monomers that each comprises of one or more single variable domains (homodimers) or of two different monomers that each comprises on or more single variable domains (heterodimers). The subject NFDs have typically altered e.g. improved binding characteristics over their monomelic counterpart. The NFDs of the invention may further be engineered through linkage by a flexible peptide or cysteines in order to improve the stability. This invention also describes conditions under which such NFDs are formed and conditions under which the formation of such dimers can be avoided.
    Type: Application
    Filed: March 2, 2010
    Publication date: April 19, 2012
    Applicant: Ablynx N.V.
    Inventors: Ann Brige, Christine Labeur, Marc Jozef Lauwereys
  • Patent number: 8129508
    Abstract: The present invention provides methods for purifying proteins. In particular, the methods employ a two-step non-affinity chromatography process without the use of an in-process tangential flow filtration step.
    Type: Grant
    Filed: March 21, 2006
    Date of Patent: March 6, 2012
    Assignee: Medarex, Inc.
    Inventors: Alahari Arunakumari, Gisela Maria Marques Ferreira
  • Publication number: 20120053325
    Abstract: 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: Application
    Filed: March 4, 2010
    Publication date: March 1, 2012
    Applicant: Biogen Idec MA Inc.
    Inventors: Robert S. Gronke, Héctor Zaanoni
  • Patent number: 8124743
    Abstract: The present invention discloses a method of purifying bivalent antibodies or antibody fragments that are active at both Fab sites from a source of antibodies or antibody fragments using a non-chromatographic method that includes inducing the formation of cyclic immunoglobulin aggregates by addition of multivalent hapten to a salt solution of soluble antibodies or antibody fragments, wherein the multivalent hapten possesses a linker between the two haptens effective to prevent the binding of both haptens of the ligand to the same antibody or antibody fragment.
    Type: Grant
    Filed: June 1, 2007
    Date of Patent: February 28, 2012
    Assignee: President and Fellows of Harvard College
    Inventors: Vijay M. Krishnamurthy, Lara A. Estroff, Vincent Semetey, Samuel W. Thomas, George K. Kaufman, Zihni Basar Bilgicer, George M. Whitesides
  • Patent number: 8114832
    Abstract: The invention relates to the detection and/or removal of conformationally altered proteins and/or molecules comprising a cross-? structure from a pharmaceutical composition. Disclosed is that unwanted and/or toxic side effects of pharmaceuticals are caused by proteins present in the pharmaceutical and adopting a cross-? structure conformation. Further disclosed is a method for detecting a protein in a pharmaceutical composition, the method comprising: contacting the pharmaceutical composition or any of its constituents comprising a protein with at least one cross-? structure-binding compound resulting in a bound protein and/or peptide comprising a cross-? structure and; detecting whether bound protein and/or peptide comprising a cross-? structure are present in the pharmaceutical composition or any of its constituents comprising a protein. Further described are methods for removing cross-? structures from a pharmaceutical composition and controlling the manufacture of a pharmaceutical composition.
    Type: Grant
    Filed: July 13, 2005
    Date of Patent: February 14, 2012
    Assignee: Crossbeta Biosciences B.V.
    Inventors: Martijn Frans Ben Gerard Gebbink, Barend Bouma
  • Patent number: 8093364
    Abstract: Methods are disclosed for use of apatite chromatography, particularly without reliance upon phosphate gradients, for purification or separation of at least one intact non-aggregated antibody, or at least one immunoreactive antibody fragment, from an impure preparation. Integration of such methods into multi-step procedures with other fractionation methods are additionally disclosed.
    Type: Grant
    Filed: January 16, 2009
    Date of Patent: January 10, 2012
    Assignee: Bio-Rad Laboratories, Inc.
    Inventor: Peter S. Gagnon
  • Publication number: 20110293594
    Abstract: The present invention provides novel methods for reducing the serine protease and/or serine protease zymogen content of a plasma-derived protein composition. Also provided are methods for manufacturing plasma-derived protein compositions having reduced serine protease and\or serine protease zymogen content. Among yet other aspects, the present invention provides aqueous and lyophilized compositions of plasma-derived proteins having reduced serine protease and/or serine protease zymogen content. Yet other aspects include methods for treating, managing, and/or preventing a disease comprising the administration of a plasma-derived protein composition having a reduced serine protease or serine protease zymogen content.
    Type: Application
    Filed: May 26, 2011
    Publication date: December 1, 2011
    Applicants: Baxter Healthcare S.A., Baxter International Inc.
    Inventors: Wolfgang Teschner, Hans-Peter Schwarz, Ruth Madlener, Sonja Svatos, Azra Pljevljakovic, Alfred Weber
  • Patent number: 8063189
    Abstract: The invention provides methods for isolating proteins in purified form from mixtures by precipitation with citrate. The methods are advantageous in that they effectively separate a protein from lower molecular weight contaminants, including fragments or portions of the protein. Such methods are particularly useful for purifying antibodies from mixtures containing antibody proteolytic fragments and unpaired chains.
    Type: Grant
    Filed: April 13, 2010
    Date of Patent: November 22, 2011
    Assignee: Bristol-Myers Squibb Company
    Inventors: Alahari Arunakumari, Gisela M. Ferreira
  • Patent number: 8058407
    Abstract: The present invention provides a method of removing product-related inactive or partially active species, high molecular weight aggregates, as well as other process-related impurities from preparations of acidic proteins by using ceramic hydroxyapatite chromatography.
    Type: Grant
    Filed: October 29, 2009
    Date of Patent: November 15, 2011
    Assignee: Wyeth LLC
    Inventors: Shujun Sun, Yin Luo, Priscilla Jennings
  • Patent number: 8017740
    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.
    Type: Grant
    Filed: February 19, 2010
    Date of Patent: September 13, 2011
    Assignee: Bio-Rad Laboratories, Inc.
    Inventor: Peter S. Gagnon
  • Patent number: 7973150
    Abstract: Disclosed are compositions and methods for producing fusion proteins with reduced immunogenicity. Fusion proteins of the invention include a junction region having an amino acid change that reduces the ability of a junctional epitope to bind to MHC Class II, thereby reducing its interaction with a T-cell receptor. Methods of the invention involve analyzing, changing, or modifying one or more amino acids in the junction region of a fusion protein in order to identify a T-cell epitope and reduce its ability to interact with a T cell receptor. Compositions and methods of the invention are useful in therapy.
    Type: Grant
    Filed: September 1, 2009
    Date of Patent: July 5, 2011
    Assignee: Merck Patent GmbH
    Inventors: Stephen D. Gillies, Jeffrey Way, Anita A. Hamilton
  • Publication number: 20110144302
    Abstract: The invention provides an immunoglobulin G Fc region binding polypeptide, which polypeptide comprises an immunoglobulin G Fc region binding motif, BM, consisting of an amino acid sequence selected from: i) EQQX4AFYEIL HLPNL-TEX18QX20X21AFIX25X26LRX29, and ii) an amino acid sequence which has at least 85% identity to the sequence defined in i). Also provided are methods of isolation or production of IgG Fc-containing molecules.
    Type: Application
    Filed: September 24, 2008
    Publication date: June 16, 2011
    Inventors: Anders Jarstad, Thomas Bergman, Lars Abrahmsen, Christofer Lendel, Karin Nord
  • Patent number: RE43655
    Abstract: 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 affect 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: Grant
    Filed: October 17, 2007
    Date of Patent: September 11, 2012
    Assignee: Bayer HealthCare LLC
    Inventors: Wytold R. Lebing, Douglas C. Lee, Klaus-Peter Radtke, Scott A. Cook, Hanns-Ingolf Paul, Patricia Alred