Blood Coagulation Factor Viii, Ahf Patents (Class 530/383)
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Patent number: 6228613Abstract: There are disclosed a stable factor VIII/vWF-complex, particularly comprising high-molecular vWF multimers, being free from low-molecular vWF molecules and from proteolytic vWF degradation products, as well as a method of producing this complex.Type: GrantFiled: November 6, 1998Date of Patent: May 8, 2001Assignee: Baxter AktiengesellschaftInventors: Bernhard Fischer, Artur Mitterer, Friedrich Dorner, Johann Eibl
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Patent number: 6214975Abstract: A chemiluminescence-based gel assay may be used as an indicator of fermenter health. The assay is performed using a sample of fermentation medium essentially directly from the fermenter (with no need for complicated purification of the sample before performing the assay). Results from the assay may be correlated with the final product purification yield of a given protein/purification protocol system. This may then be used as a predictor of purification yield before actually performing the purification.Type: GrantFiled: December 17, 1999Date of Patent: April 10, 2001Assignee: Bayer CorporationInventors: Michael Zachariou, Jonathan Mazer, Hyun J. Park, Charles Olson
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Patent number: 6211344Abstract: The invention relates to a process for preparing factor V-deficient plasma, in particular a factor V-deficient plasma from a starting plasma using antibodies, and a deficient plasma which is obtained in this way.Type: GrantFiled: August 21, 1997Date of Patent: April 3, 2001Assignee: Dade Behring Marburg GmbHInventors: Michael Kraus, Erika Aillaud, Heinz-Hermann Drescher
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Patent number: 6191256Abstract: Peptides that have domains that bind to recombinant factor VIII (rFVIII) are disclosed. A method of rFVIII binding assay using the peptides deduced from a combinatorial library in a filtration plate process is described. A method of using peptides having these available binding domains in an affinity chromatography process to purify factor VIII is also taught.Type: GrantFiled: November 20, 1998Date of Patent: February 20, 2001Assignee: Bayer CorporationInventors: Li Ang Chen, Joseph A. Buettner, Ruben G. Carbonell
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Patent number: 6180371Abstract: Specific amino acid loci of human factor VIII interact with inhibitory antibodies of hemophilia patients who have developed such antibodies after being treated with factor VIII. Modified factor VIII is disclosed in which the amino acid sequence is changed by a substitution at one or more of the specific loci. The modified factor VIII is not inhibited by inhibitory antibodies against the A2 or C2 domain epitopes. The modified factor VIII is useful for hemophiliacs, either to avoid or prevent the action of inhibitory antibodies.Type: GrantFiled: March 10, 1998Date of Patent: January 30, 2001Assignee: Emory UniversityInventor: John S. Lollar
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Patent number: 6171825Abstract: Recombinant Factor VIII can be produced in relatively large quantities on a continuous basis from mammalian cells in the absence of any animal-derived proteins such as albumin by culturing the cells in a protein free medium supplemented with polyol copolymers, preferably in the presence of trace metals such as copper. In very preferred embodiments, the medium includes a polyglycol known as Pluronic F-68, copper sulfate, ferrous sulfate/EDTA complex, and salts of trace metals such as manganese, molybdenum, silicon, lithium and chromium. With an alternative medium which included trace copper ions alone (without polyol copolymers) we were also able to enhance the productivity of Factor VIII in recombinant cells such as BHK cells that are genetically engineered to express Factor VIII.Type: GrantFiled: September 4, 1998Date of Patent: January 9, 2001Assignee: Bayer CorporationInventors: Sham-Yuen Chan, Kathleen Harris
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Patent number: 6156734Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.Type: GrantFiled: October 8, 1999Date of Patent: December 5, 2000Assignee: Eli Lilly and CompanyInventors: Brian William Grinnell, Daniel Lawrence Hartman, Sau-Chi Betty Yan
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Patent number: 6150505Abstract: The present invention provides fibrin microbeads that are biologically active and comprise extensively cross-linked fibrin(ogen) without using glutaraldehyde, and a method for preparing the fibrin microbeads. The present invention also provides a composition comprising cells bound to the fibrin microbeads, and methods for culturing and separating cells using the fibrin microbeads of the present invention. Finally, the present invention provides methods for transplanting cells and engineering tissue using the fibrin microbeads of the present invention.Type: GrantFiled: September 19, 1997Date of Patent: November 21, 2000Assignee: Hadasit Medical Research Services & Development Ltd.Inventors: Gerard Marx, Raphael Gorodetsky
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Patent number: 6143179Abstract: The invention concerns a process for the purification of factor VIII by affinity chromatography characterized in that a biological fluid containing factor VIII is contacted with immobilized cellular von Willebrand factor or a derivative thereof under such conditions that factor VIII is adsorbed to the immobilized von Willebrand factor or derivative thereof, impurities are separated and adsorbed factor VIII is eluted.Type: GrantFiled: December 22, 1998Date of Patent: November 7, 2000Assignee: Kerckhoff-Klinik GmbHInventors: Gert Muller-Berghaus, Bernd Potzsch, Horst Schwinn
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Patent number: 6130203Abstract: Hybrid proteins which affect blood coagulation comprise a region from a donor anticoagulant or antithrombotic protein, and the resulting hybrid protein has a modified biological activity. Information concerning the hybrid proteins implicates DNA sequences encoding the proteins and hosts, including transgenic animals, that possess these DNA sequences; antibodies directed against hybrid proteins; methods of modifying the properties of proteins; and treatment methods employing hybrid proteins.Type: GrantFiled: February 3, 1999Date of Patent: October 10, 2000Assignee: Baxter AktiengesellschaftInventor: Johannes J. Voorberg
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Patent number: 6117647Abstract: A process for determining glycosaminoglycans in antithrombin III (ATIII)-containing solutions by increasing the ionic strength of the AT III-containing solution until the interaction between AT III and glycosaminoglycans is prevented, removing the AT III which has been released from the glycosaminoglycans from the solution, and desalting and determining the glycosaminoglycan which has remained in the solution.Type: GrantFiled: August 13, 1997Date of Patent: September 12, 2000Assignee: Aventis Behring GmbHInventors: Jurgen Romisch, Harald Stauss
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Patent number: 6060447Abstract: Recombinant protein complexes having human Factor VIII:C activity are expressed in a eukaryotic host cell by transforming the host cell with first and second expression cassettes encoding a first polypeptide substantially homologous to human Factor VIII:C A domain and a second polypeptide substantially homologous to human Factor VIII:C C domain, respectively. In the present invention, the first polypeptide may be extended having at its C-terminal a human Factor VIII:C B domain N-terminal peptide, a polypeptide spacer of 3-40 amino acids, and a human Factor VIII:C B domain C-terminal peptide. Expression of the second polypeptide is improved by employing an .alpha..sub.1 -antitrypsin signal sequence.Type: GrantFiled: May 16, 1995Date of Patent: May 9, 2000Assignees: Chiron Corporation, Novo Nordisk A/SInventors: Barbara Chapman, Rae Lyn Burke, Mirella Ezban Rasmussen, Jan Moller Mikkelson
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Patent number: 6054122Abstract: This invention provides a fibrin sealant dressing, wherein said fibrin sealant may be supplemented with at least one composition selected from, for example, one or more regulatory compounds, antibody, antimicrobial compositions, analgesics, anticoagulants, antiproliferatives, anti-inflammatory compounds, cytokines, cytotoxins, drugs, growth factors, interferons, hormones, lipids, demineralized bone or bone morphogenetic proteins, cartilage inducing factors, oligonucleotides polymers, polysaccharides, polypeptides, protease inhibitors, vasoconstrictors or vasodilators, vitamins, minerals, stabilizers and the like. Also disclosed are methods of preparing and/or using the unsupplemented or supplemented fibrin sealant dressing.Type: GrantFiled: June 7, 1995Date of Patent: April 25, 2000Assignee: The American National Red CrossInventors: Martin James MacPhee, William Nash Drohan, Christoper J. Woolverton
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Patent number: 6051418Abstract: Hybrid proteins which affect blood coagulation comprise a region from a donor anticoagulant or antithrombotic protein, and the resulting hybrid protein has a modified biological activity. Information concerning the hybrid proteins implicates DNA sequences encoding the proteins and hosts, including transgenic animals, that possess these DNA sequences; antibodies directed against hybrid proteins; methods of modifying the properties of proteins; and treatment methods employing hybrid proteins.Type: GrantFiled: February 3, 1999Date of Patent: April 18, 2000Assignee: Immuno AGInventor: Johannes J. Voorberg
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Patent number: 6048720Abstract: Processes for improving the in vivo function of factor VIII by shielding exposed targets of the factor VIII comprise a) immobilizing the factor VIII by interaction with a group-specific adsorbent carrying ligands manufactured by organic-chemical synthesis, for preventing polymer coupling to reactive amino acids of the immobilized factor VIII, within or adjacent to interaction domains; b) activating a biocompatible polymer; c) conjugating the activated biocompatible polymer to external sites of the immobilized factor VIII; and thereafter d) eluting the conjugate from the adsorbent. Processes for administering factor VIII comprise subcutaneously, intramuscularly, intradermally or intravenously administering a conjugate of factor VIII and a biocompatible polymer, and methods for treatment of hemophilia A comprise subcutaneous, intramuscular, intradermal or intravenous administration of a conjugate of factor VIII and a biocompatible polymer.Type: GrantFiled: May 21, 1998Date of Patent: April 11, 2000Assignee: Pharmacia & Upjohn ABInventors: Johanna Dalborg, Helena Sandberg, Anna-Lisa Smeds, Eva kerblom
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Patent number: 6037452Abstract: Factor VIIIC:vWF, Factor VIII C, Factor IX or Factor IX or the activated co-factors thereof are covalently linked to a poly(alkylene oxide).Type: GrantFiled: April 10, 1992Date of Patent: March 14, 2000Assignee: Alpha Therapeutic CorporationInventors: Hitoshi Minamino, Edward H. Mealey
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Patent number: 6019993Abstract: A two-component fibrin glue for human application includes a) a component A containing i) a virus-inactivated and concentrated cryoprecipitate that contains fibrinogen, and ii) tranexamic acid or a pharmaceutically acceptable salt, thereof; and b) component B containing a proteolytic enzyme that, upon combination with component A, cleaves, specifically, fibrinogen present in the cryoprecipitate of component A, thereby, effecting a fibrin polymer.Type: GrantFiled: November 30, 1995Date of Patent: February 1, 2000Assignee: Omrix Biopharmaceuticals S.A.Inventor: Frederic Bal
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Patent number: 6008199Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.Type: GrantFiled: October 16, 1998Date of Patent: December 28, 1999Assignee: Eli Lilly and CompanyInventors: Brian William Grinnell, Daniel Lawrence Hartman, Sau-Chi Betty Yan
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Patent number: 6005082Abstract: The present invention relates to a process for purifying recombinant coagulation factor VIII by loading an aqueous solution containing factor VIII onto a hydrophobic interaction chromatography (HIC) gel, wherein at least one surfactant is present in the aqueous solution and/or a buffer solution used to equilibrate the gel prior to loading the aqueous solution onto the gel. The presence of a surfactant when loading the solution containing factor VIII onto the HIC gel, makes it possible to efficiently separate the intact and active factor VIII molecules from molecules with structural deviations. With the present invention it is further possible to reduce the content of DNA and/or CHO cell contaminants considerably and increase the activity of the factor VIII product to a hitherto unknown extent.Type: GrantFiled: March 27, 1997Date of Patent: December 21, 1999Assignee: Genetics Institute, Inc.Inventor: Anna-Lisa Smeds
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Patent number: 6004555Abstract: Disclosed are various compositions and methods for use in achieving specific blood coagulation. This is exemplified by the specific in vivo coagulation of tumor vasculature, causing tumor regression, through the site-specific delivery of a coagulant using a bispecific antibody.Type: GrantFiled: June 7, 1995Date of Patent: December 21, 1999Assignees: Board of Regents, The University of Texas System, The Scripps Research InstituteInventors: Philip E. Thorpe, Thomas S. Edgington
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Patent number: 6005077Abstract: The invention relates to the use of von Willebrand Factor (vWF) with a prolonged biological half-life for the production of a preparation for stabilization of blood coagulation Factor VIII (FVIII:C) in a mammal. Additionally, a pharmaceutical preparation is provided comprising a biologically active FVIII:C/vWF complex with improved pharmokinetic properties, said complex containing a vWF with a prolonged biological half-life.Type: GrantFiled: November 6, 1996Date of Patent: December 21, 1999Assignee: Immuno AktiengesellschaftInventors: Hans-Peter Schwarz, Peter Turecek, Johann Eibl
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Patent number: 5994310Abstract: Peptides which bind Factor VIII are disclosed. The peptides have available Factor VIII binding domains having a Trp-His-Tyr-Tyr-His-Gly, His-Ile-Gln-His-Tyr-His, or His-Gln-Tyr-Gly-Tyr-His sequence. Peptides having at least one of these Factor VIII binding domains are immobilized upon a chromatographic substrate in a preferred embodiment of the invention. This preferred embodiment is useful in a chromatography process to purify human Factor VIII.Type: GrantFiled: September 3, 1998Date of Patent: November 30, 1999Assignee: Bayer CorporationInventors: Joseph A. Buettner, June P. Davis
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Patent number: 5972885Abstract: A pharmaceutical formulation for subcutaneous, intramuscular or intradermal administration comprising recombinant coagulation factor VIII and use thereof for manufacture of a medicament for treating haemophilia is provided. The formulation comprises a highly purified recombinant coagulation factor VIII in a concentration of at least 1000 IU/ml, which gives surprisingly high levels of active factor VIII in the blood stream after subcutaneous, intramuscular or intradermal administration. The formulation is intended for treatment of haemophilia by subcutaneous, intramuscular or intradermal administration. The recombinant factor VIII is preferably a deletion derivative thereof, which can be used for the manufacture of a medicament for subcutaneous administration.Type: GrantFiled: December 21, 1995Date of Patent: October 26, 1999Assignee: Pharmacia & Upjohn AktiebolagInventors: Jack Spira, Lars Widlund, Thomas Osterberg
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Patent number: 5962405Abstract: The invention relates to storage-stable fibrinogen preparations for preparing concentrated fibrinogen solution for use as a tissue adhesive or for preparing fibrinogen solutions for other uses, for example, for infusion purposes. The fibrinogen preparations are characterized in that(i) the lyophilized preparation comprises a substance improving the solubility of fibrinogen such that the reconstitution time is up to 15 minutes, preferably less than 7 minutes, when dissolving with water at room temperature to a solution with a fibrinogen concentration of at least 70 mg/ml and(ii) the ready-to-use tissue adhesive solution obtained from the preparation forms fibrin clots having physiological fibrin structure after mixing with a thrombin-CaCl.sub.2 solution.Type: GrantFiled: April 23, 1997Date of Patent: October 5, 1999Assignee: Immuno AktiengesellschaftInventor: Thomas Seelich
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Patent number: 5962650Abstract: The present invention relates to a final drug product comprising coagulation factor VIII in an aqueous solution with a reduced concentration of oxygen. In this way, the factor VIII activity can be retained during storage to a surprisingly high degree. The factor VIII activity can be retained for a prolonged period of time, if the final drug product further comprises an inert gas and/or an antioxidant. The present invention also relates to processes for reducing the oxygen concentration of the aqueous solution, and a method for improving the stability of factor VIII in an aqueous solution by storing the solution under an inert gas atmosphere. By the present invention it is possible to retain at least 50% of the initial activity of factor VIII after storage for at least 6 months at a temperature of 2 to 10.degree. C. and a pH of the solution of 6.5 to 8.5.Type: GrantFiled: October 30, 1995Date of Patent: October 5, 1999Assignee: Pharmacia & Upjohn AktiebolagInventors: Thomas Osterberg, Angelica Fatouros
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Patent number: 5958716Abstract: The present invention provides a method for indicating von Willebrand factor deficiency in a blood sample or platelet-rich plasma sample which exhibits abnormal platelet function comprising (a) adding a von Willebrand factor preparation to the sample, and (b) testing the sample for platelet function. In this method, the von Willebrand factor preparation restores normal platelet function and indicates that the sample initially lacked the von Willebrand factor. The von Willebrand factor preparation comprises purified von Willebrand factor. The invention also discloses a method which further comprises separating the blood sample into a plasma layer and cellular component layer and removing the plasma layer, prior to the step of adding a von Willebrand factor preparation to the sample. In this embodiment the von Willebrand factor preparation comprises platelet-poor plasma containing a normal level of von Willebrand factor.Type: GrantFiled: June 6, 1996Date of Patent: September 28, 1999Assignee: Dade Behring Inc.Inventor: Sourav K. Kundu
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Patent number: 5952198Abstract: Recombinant Factor VIII expression in a mammalian cell culture can be increased by including a novel liposome-like substance in the culture medium. The liposome-like substance comprises at least two (preferably at least three) different lipids in defined molar ratios. In a preferred embodiment, the addition of a liposome-like substance comprised of dioleoyl phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine in a molar ratio of 4:1:1 to the culture medium of GS-MDR cells resulted in an increase in FVIII production by a factor greater than five.Type: GrantFiled: April 17, 1996Date of Patent: September 14, 1999Assignee: Bayer CorporationInventor: Sham-Yuen Chan
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Patent number: 5951583Abstract: A procoagulant designed to effect hemostasis at a puncture site in a patient's vasculature without the aid of manual compression is comprised of lyoplilized thrombin that is reconstituted with a buffered diluent and collagen that is mixed with the reconstituted thrombin to produce a viscous mixture. The buffered diluent is preferably of sodium phosphate and water. The procoagulant is essentially isotonic and has a pH in the range of 5-10. The method of making the procoagulant is comprised of the steps of reconstituting the lyophilized thrombin with the buffered diluent and then, mixing the reconstituted thrombin with collagen to both reduce the size of the particles of the collagen and form a fluid mixture.Type: GrantFiled: February 27, 1998Date of Patent: September 14, 1999Assignee: Vascular Solutions, Inc.Inventors: Todd L. Jensen, Gary Gershony
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Patent number: 5948407Abstract: Disclosed is a method for reducing an immune response to a parenterally administered non-autologous antigen in an individual who is immunologically responsive thereto by mucosally administering to the individual an amount of the antigen effective to reduce any immune response to parenteral administration of said antigen. The antigen can be a polypeptide such as a hormone, like insulin, which supplements a metabolic deficiency in the recipient of a polypeptide intended to serve the same function. The polypeptide can also be one which supplements a deficiency in the production of a physiologically important polypeptide, such as a hematologic regulatory factor. The hematologic regulatory factor can enhance or inhibit thrombogenesis or platelet deposition. Also, the antigen can be a tissue or cell preparation, such as of allogeneic or xenogeneic tissue or cells.Type: GrantFiled: March 18, 1998Date of Patent: September 7, 1999Assignee: Shire Laboratories Inc.Inventors: Charlotte M. McGuinness, Beth A. Burnside, Edward M. Rudnik
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Patent number: 5925738Abstract: The present invention relates to the preparation and use of liquid formulations of plasma proteins, particularly blood coagulation factors. More specifically, the present invention relates to stable liquid formulations of Factor VIII and Factor IX that can be administered by injection or infusion to provide a constant level of the coagulation factor in the blood.Type: GrantFiled: November 29, 1996Date of Patent: July 20, 1999Assignees: The American National Red Cross, The Coalition for Hemophilia BInventors: Shirley I. Miekka, William N. Drohan, Thomas R. Jameson, Manish P. Singh, John R. Taylor, Jr., Martin J. MacPhee
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Patent number: 5925739Abstract: The present invention relates to a pharmaceutical formulation for subcutaneous, intramuscular or intradermal administration comprising coagulation factor VIII or factor IX and use thereof for manufacture of a medicament for treating haemophilia A or B. The formulation comprises coagulation factor VIII or factor IX with an activity of at least 200 IU/ml and an additive increasing the bio-availability of factor VIII or factor IX. Tests with factor VIII gives a therapeutic level of active factor VIII in the blood stream for a surprisingly long period of time after subcutaneous, intramuscular or intradermal administration. The factor VIII is suitably a highly purified recombinant factor VII, and preferably a deletion derivative thereof, which can be used for the manufacture of a medicament for subcutaneous administration.Type: GrantFiled: September 17, 1996Date of Patent: July 20, 1999Assignee: Pharmacia & Upjohn ABInventors: Jack Spira, Lars Widlund, Thomas Osterberg, Brita Sjostrom, Marianne Mikaelsson
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Patent number: 5919766Abstract: The present invention relates to a novel composition comprising coagulation Factor VIII and a non-ionic surfactant such as block co-polymers, e.g. polyoxamers or polyoxyethylene (20) fatty acid esters e.g. polysorbate 20 or polysorbate 80 as a stabilizer. The composition can also comprise sodium chloride, calcium chloride, L-histidine and/or sugars or sugar alcohols.Type: GrantFiled: May 27, 1997Date of Patent: July 6, 1999Assignee: Pharmacia & Upjohn AktiebolagInventors: Thomas Osterberg, Angelica Fatouros
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Patent number: 5919908Abstract: A final drug product comprises a plasma protein selected from the group consisting of coagulation factor VIII and factor IX, in an aqueous solution. The concentration of oxygen in the solution is reduced and/or the solution contains an antioxidant. The solution further contains a carbohydrate in a concentration of at least 350 mg/ml. The protein activity after storage for at least 6 months at a temperature of from 0.degree. C. to 40.degree. C. is from 70% to 130% of its initial value. In a process for preparing the final drug product and a method for improving the long-term stability of coagulation factor VIII or factor IX in an aqueous solution, a carbohydrate is included in the solution in a concentration of at least 350 mg/ml and the solution is stored in its final container under an oxygen-reduced atmosphere or includes an antioxidant.Type: GrantFiled: November 26, 1997Date of Patent: July 6, 1999Assignee: Pharmacia & Upjohn ABInventors: Thomas Osterberg, Angelica Fatouros
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Patent number: 5919909Abstract: A process for the preparation of factor IX from a biological source by chromatography involves prior treatment with ammonium sulfate as a protein precipitant at a concentration of from 1.5-2.3 mol/l.Type: GrantFiled: November 26, 1997Date of Patent: July 6, 1999Assignee: Octapharma AGInventors: Djuro Josic, Lutz Hoffer, Frank Morfeld
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Patent number: 5912328Abstract: In order to separate viruses from protein solutions, particles of a solid phase are suspended in said protein solution. The solid phase is an adsorbent chosen from the group kieselguhr, silicic acid, clay minerals, metal hydroxide or oxihydrate, cellulose, perlite, and water insoluble synthetic polymers. Subsequently the solid phase together with the viruses that have adsorbed to it is separated from the fluid phase. The protein solution is brought into contact at least once with the solid phase for at least 10 minutes during which time a suspension is formed; subsequently the solid phase is separated from the liquid phase.Type: GrantFiled: October 7, 1997Date of Patent: June 15, 1999Assignee: Rotkreuzstiftung Zentrallaboratorium BlutspendedienstInventors: Adames Omar, Jean-Jacques Morgenthaler
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Patent number: 5910481Abstract: Hybrid proteins which affect blood coagulation comprise a region from a donor anticoagulant or antithrombotic protein, and the resulting hybrid protein has a modified biological activity. Information concerning the hybrid proteins implicates DNA sequences encoding the proteins and hosts, including transgenic animals, that possess these DNA sequences; antibodies directed against hybrid proteins; methods of modifying the properties of proteins; and treatment methods employing hybrid proteins.Type: GrantFiled: November 13, 1995Date of Patent: June 8, 1999Assignee: Immuno AGInventor: Johannes J. Voorberg
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Patent number: 5907032Abstract: A process for preparing thrombin which comprises treating a mixture comprising prothrombin, factor Xa, factor Va, and phospholipids with calcium ions, at a pH of 6.0-7.0 is provided. In particular the pH of 6.0-7.0 may be generated by the addition of the calcium ions or by buffering the preparation to a pH of 6.0-7.0. Thrombin preparations so produced may be subjected to further purification and are particularly stable even when substantially free of exogenous stabilizing agents such as proteins, sugars, polyol and mixtures thereof, and may be subject to freeze-drying and a virus inactivation by heat treatment.Type: GrantFiled: November 20, 1997Date of Patent: May 25, 1999Assignee: Common Services AgencyInventors: Ian Randle MacGregor, John Charles Hardy, Olive Drummond
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Patent number: 5892005Abstract: The invention provides high and low molecular weight fraction of von Willebrand Factor (vWF), which can be obtained by absorbing vWF to a heparin affinity support followed by eluting the vWF at differing salt concentrations.Type: GrantFiled: December 19, 1996Date of Patent: April 6, 1999Assignee: Immuno AktiengesellschaftInventors: Bernhard Fischer, Artur Mitterer, Friedrich Dorner
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Patent number: 5888974Abstract: A hybrid procoagulant factor VIII is produced by isolation and recombination of human and other nonhuman mammalian factor VIII subunits or domains, or by genetic engineering of the human and animal factor VIII genes. Subunits or domains of factor VIII that have been purified from human or animal plasma are isolated, and hybrid human/animal factor VIII is produced by (1) mixing either animal heavy chain subunits with human light chain subunits or by mixing human heavy chain subunits with animal light chain subunits, thereby producing human light chain/animal heavy chain and human heavy chain/animal light chain hybrid molecules; or by (2) mixing one or more domains of one species with one or more domains of the other species. These hybrid molecules are isolated by ion exchange chromatography.Type: GrantFiled: June 7, 1995Date of Patent: March 30, 1999Assignee: Emory UniversityInventors: John S. Lollar, Marschall S. Runge
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Patent number: 5880265Abstract: The invention relates to a method for isolation of highly pure von Willebrand Factor in which recombinant von Willebrand Factor (rvWF) is chromatographically purified by anion exchange chromatography on an anion exchanger of the quaternary amino type in a buffer solution comprising buffer substances and optionally salt.The buffer solutions are preferably free of stabilizers, amino acids and other additives. According to this method, highly pure recombinant vWF can be obtained, which is free from blood plasma proteins, especially free from Factor VIII, and is physiologically active.Further, the invention relates to a pharmaceutical preparation that contains rvWF, which is comprised of multimers with a high structural integrity.Type: GrantFiled: July 22, 1997Date of Patent: March 9, 1999Assignee: Immuno AktiengesellschaftInventors: Bernhard Fischer, Artur Mitterer, Friedrich Dorner, Hans-Peter Schwarz, Peter Turecek, Johann Eibl, Falko-Guenter Falkner, Uwe Schlokat, Wolfgang Mundt, Manfred Reiter, Renate Den-Bouwmeester
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Patent number: 5877281Abstract: The present invention relates to a member of a novel gene family referred to as developmentally-regulated endothelial cell locus-1 (del-1). In particular, the invention relates to del-1 nucleotide sequences, Del-1 amino acid sequences, methods of expressing a functional gene product, and methods of using the gene and gene product.Type: GrantFiled: June 5, 1996Date of Patent: March 2, 1999Assignees: Progenitor, Inc., Vanderbilt UniversityInventors: Thomas Quertermous, Brigid Hogan, H. Ralph Snodgrass, Thomas Joel Zupancic
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Patent number: 5874408Abstract: A stable albumin-free Recombinant Factor VIII (rFVIII) formulation in lyophilized form having both crystalline and amorphous components and comprising, when reconstituted with water, about 65 to 400 mM glycine, up to 50 mM histidine, 15 to 60 mM sucrose, up to 50 mM NaCl (up to 100 mM NaCl if cake appearance not critical), up to 5 mM CaCl.sub.2 and 50 to 1500 lU/ml of rFVIII. A very preferred formulation comprises upon reconstitution with water about 290 mM glycine, 20 mM histidine, 30 mM sucrose, 30 mM NaCl, 2.5 mM CaCl.sub.2 and 50 to 1500 lU/ml of rFVIII. The residual water content of the lyophilized preparation is about 1 to 3% by weight, preferably about 1% by weight.Type: GrantFiled: May 28, 1998Date of Patent: February 23, 1999Assignee: Bayer CorporationInventor: Rajiv Nayar
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Patent number: 5872099Abstract: The present invention relates to a method for separation of vWF into high molecular vWF and low molecular vWF which is characterized in that vWF is bound to an affinity support and is then eluted at different salt concentrations.Type: GrantFiled: December 19, 1996Date of Patent: February 16, 1999Assignee: Immuno AktiengesellschaftInventors: Bernhard Fischer, Arthur Mitterer, Friedrich Dorner
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Patent number: 5869292Abstract: Hybrid proteins which affect blood coagulation comprise a region from a donor anticoagulant or antithrombotic protein, and the resulting hybrid protein has a modified biological activity. Information concerning the hybrid proteins implicates DNA sequences encoding the proteins and hosts, including transgenic animals, that possess these DNA sequences; antibodies directed against hybrid proteins; methods of modifying the properties of proteins; and treatment methods employing hybrid proteins.Type: GrantFiled: June 25, 1997Date of Patent: February 9, 1999Assignee: Immuno AGInventor: Johannes J. Voorberg
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Patent number: 5869617Abstract: The invention provides high and low molecular weight fraction of von Willebrand Factor (vWF), which can be obtained by absorbing vWF to a heparin affinity support followed by eluting the vWF at differing salt concentrations The low molecular weight fraction is predominantly dimers and tetramers, and the high molecular weight fraction is predominantly larger multimers.Type: GrantFiled: October 4, 1995Date of Patent: February 9, 1999Assignee: Immuno AktiengesellschaftInventors: Bernhard Fischer, Artur Mitterer, Friedrich Dorner
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Patent number: 5863896Abstract: The present invention provides methods, reagents, and test kits for evaluating the effect of a test composition on APC response by employing factor Va.sup.R506Q Methods and compositions for treating patients suffering from reduced APC response are also provided.Type: GrantFiled: November 9, 1995Date of Patent: January 26, 1999Assignee: Immuno AGInventors: Jan Rosing, Guido Tans, Katalin Varadi, Hans Peter Schwarz
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Patent number: 5859204Abstract: Site-specific replacement of amino acids in the region of positions 484-509 of human factor VIII can result in reduction of reactivity to an inhibitory antibody while procoagulant activity is retained. Modified human factor VIII having an immunoreactivity-reducing amino acid substituted for the naturally occurring amino acid is described.Type: GrantFiled: June 26, 1996Date of Patent: January 12, 1999Assignee: Emory UniversityInventor: John S. Lollar
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Patent number: 5849536Abstract: The subject invention provides non-glycosylated, biologically active polypeptides which comprise the vWF (von Willebrand Factor) GP1b binding domain. These polypeptides may be used to inhibit platelet adhesion and aggregation in the treatment of subjects with conditions such as cerebrovascular disorders and cardiovascular disorders. This invention also provides expression plasmids encoding these polypeptides as well as methods of producing by transforming a bacterial cell and recovering such polypeptides. In addition, the subject invention provides methods of treating and preventing cerebrovascular, cardiovascular and other disorders using these polypeptides to inhibit platelet aggregation.Type: GrantFiled: November 30, 1994Date of Patent: December 15, 1998Assignee: Bio-Technology General Corp.Inventors: Leonard Garfinkel, Tamar Richter
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Patent number: 5847086Abstract: Processes for preparing aqueous solutions of cysteine-altered von Willebrand Factor fragment which are substantially free of aggregate and capable of therapeutic use for treating thrombosis are provided. The claimed process comprises providing an aqueous solution of vWF fragment and denaturant and containing undesired contaminants, said solution having an acidic pH; separating said contaminants from said solution by contacting said solution with an affinity chromatography medium to which said vWF fragments adhere; eluting said vWF fragment from said affinity chromatography medium in the presence of the denaturant; and separating the eluted fragment from said denaturant while maintaining the aqueous solution of the fragment at a pH of about 2.5 to less than about 5.5 to increase monomerization of, and decrease aggregation of, said fragment, thereby forming an aqueous solution of vWF fragment which is substantially free of aggregate.Type: GrantFiled: June 7, 1995Date of Patent: December 8, 1998Assignee: Centeon L.L.C.Inventors: David L. Farb, Michael E. Hrinda, Ted C. K. Lee, Christopher P. Prior, David Weber
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Patent number: 5834420Abstract: A fibrinogen concentrate has a purity of 98% or higher and is free of viral contaminants and proteases. The fibrinogen concentrate is obtained by subjecting a solubilized plasma fraction containing fibrinogen to a viral inactivation chemical treatment using a solvent/detergent, subjecting the resulting viral-inactivated fraction to precipitation in a solution containing an amino acid at an acidic pH to obtain a supernatant, filtering the supernatant to obtain a purified fibrinogen concentrate, and recovering the purified fibrinogen concentrate.Type: GrantFiled: July 7, 1997Date of Patent: November 10, 1998Assignee: Croix-Rouge de BelgiqueInventors: Ruth Laub, Luc De Wael