Thrombin Patents (Class 435/214)
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Patent number: 8062876Abstract: Methods for converting prethrombin-1 to thrombin are disclosed. An aqueous solution of prethrombin-1 is applied to oscutarin-C immobilized on a solid support so as to provide from 500 mg to 4000 mg of prethrombin-1 per mL of the solid support and a contact time between the prethrombin-1 and the oscutarin-C of from 1.8 to 3.5 minutes. The resulting active thrombin may be captured on an ion exchange chromatography medium or an affinity chromatography medium.Type: GrantFiled: December 21, 2006Date of Patent: November 22, 2011Assignee: Zymogenetics, Inc.Inventors: Robert W. Mallett, Christopher J. Stenland, Jonathon C. Boone, John W. Forstrom, Karen S. De Jongh
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Patent number: 8043629Abstract: A safe and effective hemostatic is provided. The invention relates to a bioabsorbable synthetic nonwoven fabric holding thrombin as an effective ingredient and a hemostatic comprising said bioabsorbable synthetic nonwoven fabric. The bioabsorbable synthetic nonwoven fabric holding thrombin in accordance with the present invention may be prepared by a process which comprises the steps of immersing a bioabsorbable synthetic nonwoven fabric into a solution containing thrombin and of lyophilizing the obtained nonwoven fabric. The bioabsorbable synthetic nonwoven fabric holding thrombin in accordance with the present invention allows for quicker and more effective hemostasis.Type: GrantFiled: November 16, 2007Date of Patent: October 25, 2011Assignee: Juridical Foundation The Chemo-Sero-Therapeutic Research InstituteInventors: Takanori Uchida, Noriko Shinya, Hiroshi Kaetsu, Takayuki Imamura, Chikateru Nozaki
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Patent number: 7968682Abstract: Provided are degradation-resistant fibrinogen sealants comprising a first composition comprising one or more of fibrinogen ?A/?? heterodimers and/or fibrinogen ??/?? homodimers and a second composition comprising thrombin and, optionally, degradation-resistant fibrinogen sealants disclosed herein may further comprise Factor XIII and calcium. Degradation-resistant fibrinogen sealants are suitable for the treatment of trauma, particularly vascular trauma.Type: GrantFiled: December 12, 2007Date of Patent: June 28, 2011Assignee: Oregon Health & Science UniversityInventor: David H. Farrell
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Publication number: 20110123497Abstract: The present invention provides a biocompatible, biodegradable graft composition for regeneration of neural tissue, comprising the following components: a) a gel scaffold formed from an isolated platelet containing fluid and an activating agent comprising calcium chloride, with or without thrombin, b) a nerve growth factor selected from BDNF, NGF, retinoic acid and combinations thereof, and c) a culture of at least 50,000 progenitor stem cells; the method of production and the uses thereof.Type: ApplicationFiled: November 20, 2009Publication date: May 26, 2011Applicant: FINA BIOTECH, S.L.U.Inventors: MERCEDES ZURITA CASTILLO, JESUS VAQUERO CRESPO, CONCEPCION AGUAYO FERRER, LAURA OTERO ORTEGA
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Publication number: 20110117065Abstract: This document relates to compositions containing cardiogenic factors, to methods to obtain cells by culturing initial cells in the presence of such factors; and methods of administering the obtained cells to heart tissue.Type: ApplicationFiled: May 20, 2009Publication date: May 19, 2011Inventors: Andre Terzic, Atta Behfar
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Patent number: 7927626Abstract: The present invention is directed to processes of making flowable hemostatic compositions and devices that include the flowable hemostatic composition disposed therein, where a volume of a biocompatible liquid, a volume of a biocompatible gas, and an amount of solid particles of a biocompatible polymer are mixed together to form a substantially homogenous composition including a discontinuous gas phase and the solid particles substantially homogenously dispersed throughout a continuous liquid phase to form a flowable hemostatic composition, and the composition then transferred into a device suitable for applying the flowable hemostatic composition to a site of a body requiring hemostasis under conditions effective to maintain the substantially homogeneous dispersion of the gas phase and the solid particles throughout the liquid phase.Type: GrantFiled: July 21, 2004Date of Patent: April 19, 2011Assignee: Ethicon, Inc.Inventors: Sanyog M. Pendharkar, Anne J. Gorman, Dwayne. Lee Looney, Guanghui Zhang, Ada Rivera
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Publication number: 20100254972Abstract: The invention relates to a method for selecting, isolating and/or recovering a peptide or polypeptide from a library or a repertoire of peptides and polypeptides (e.g., a display system) that is resistant to degradation by a protease such as a protease found in the GI tract or pulmonary tissue of a human. Generally, the method comprises providing a library or repertoire of peptides or polypeptides, combining the library or repertoire with a protease under conditions suitable for protease activity, and selecting, isolating and/or recovering a peptide or polypeptide that is resistant to degradation by the protease and has a desired biological activity. The selected peptides and polypeptides have utility as therapeutics, eg for treating disease or conditions of GI tract or pulmonary tissue in humans.Type: ApplicationFiled: June 3, 2008Publication date: October 7, 2010Applicant: Domantis LimitedInventors: Laurent Jespers, Malgorzata Pupecka, Ian Tomlinson, Carolyn Enever
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Patent number: 7807351Abstract: An aptamer-probe complex for detecting the presence of a target molecule is disclosed. The complex of the present invention contains an aptamer moiety which is able to bind to an indicator protein and change the properties of the indicator protein, and a probe moiety which is able to bind to a target molecule, wherein the aptamer moiety and the probe moiety are combined in such a manner that the binding mode between the aptamer moiety and the indicator protein changes when the probe moiety binds to the target molecule. A target molecule can be detected with combination of an aptamer which binds to a certain protein, and a probe which binds to the target molecule, utilizing the properties of that protein as an indicator.Type: GrantFiled: November 22, 2004Date of Patent: October 5, 2010Assignee: Techno Medica Co., Ltd.Inventors: Koji Sode, Kazunori Ikebukuro
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Publication number: 20100233783Abstract: Process for purifying a recombinant protein including one or a few procedural steps only. The process combines the step of lysis of the host cell, with the purification of the protein of interest, allowing for a rapid and much more efficient process of purification. The conditions used during the purification process are those of a high temperature and a low pH, allowing for thermostable and acid-resistant recombinant proteins to be isolated from a suspension. The invention also relates to purifying recombinant proteins which are fusion proteins, wherein one part of the protein may be selected from an enamel matrix protein, such as amelogenin.Type: ApplicationFiled: March 23, 2006Publication date: September 16, 2010Applicant: Straumann Holding AGInventors: Johan Per Henrik Svensson, Leif Bülow
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Publication number: 20100226909Abstract: A device for isolating a component of a multi-component composition. The device includes a housing, a chamber, and a withdrawal port. The chamber is rotatably mounted within the housing. The chamber includes a chamber base and a sidewall. The side wall extends from the chamber base. At least a portion of the sidewall is defined by a filter that permits passage of a first component of the multi-component composition out of the chamber through the filter and to the housing base. The filter restricts passage of a second component of the multi-component composition through the filter. The withdrawal port extends from a position proximate to the housing base to an exterior of the device. The withdrawal port permits the withdrawal of the first component from the housing base to an exterior of the device.Type: ApplicationFiled: March 6, 2009Publication date: September 9, 2010Applicant: BIOMET BIOLOGICS, LLCInventors: Barry F. Hecker, Michael D. Leach
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Patent number: 7776574Abstract: The invention relates to a thrombolytic enzyme referred to as Thrombinase having a molecular weight of 31,000 to 32,000. Such a thrombolytic enzyme can be used for dissolving blood clots. The process comprises culturing a filtrate of Bacillus sphaericus sero type H5a 5b, removing the cell, subjecting the cell supernatant to filtration, salting out the retentate, subjecting the precipitate to dialysis, reprecipitating the precipitate and then reconstituting in buffer and finally decolourizing, purifying and dialyzing.Type: GrantFiled: May 20, 2004Date of Patent: August 17, 2010Assignees: National Research Development Corporation, Malladi Drugs & Pharmaceuticals Ltd.Inventors: Perurmadom Ramaiyer Mahadevan, Sita Mahadevan, legal representative, Subrahmanyam Chivukula Sekar, Sundaramurthy Suresh Babu
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Publication number: 20100183589Abstract: The invention is directed to blood proteins produced in monocot seeds and isolated therefrom for use in therapeutic compositions, and to methods of making these isolated blood proteins and to therapeutic compositions comprising them.Type: ApplicationFiled: March 31, 2010Publication date: July 22, 2010Applicant: VENTRIA BIOSCIENCEInventors: Ning Huang, Raymond L. Rodriguez, Frank E. Hagie, David M. Stalker
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Patent number: 7718412Abstract: The present invention includes sterilized hemostatic compositions that contain a continuous, biocompatible liquid phase having a solid phase of particles of a biocompatible polymer suitable for use in hemostasis and that is substantially insoluble in the liquid phase, and sterile thrombin, each of which is substantially homogenously dispersed throughout the continuous liquid phase, and methods for making such compositions.Type: GrantFiled: July 23, 2004Date of Patent: May 18, 2010Assignee: Ethicon, Inc.Inventors: Sanyog M. Pendharkar, Anne J. Gorman
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Publication number: 20100047834Abstract: To provide a method for stabilizing unstable ?-thrombin in a thrombin-containing solution, a solution containing stabilized ?-thrombin, and a liquid fibrinogen assay reagent containing the solution. The method for stabilizing ?-thrombin in a thrombin-containing solution, which includes adjusting the percentage of ?-thrombin to 70% or more with respect to the amount of total thrombin in the thrombin-containing solution.Type: ApplicationFiled: December 6, 2007Publication date: February 25, 2010Applicant: Sekisui Medical Co., Ltd.Inventors: Remi Ikeda, Chizuru Morikawa, Hirokazu Yago
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Publication number: 20100040597Abstract: A thrombin mutant in which at least serine at position 205 among amino acids in the active center of the thrombin B chain has been replaced with another amino acid, and further at least one of the following replacements have been introduced: (I) replacement of arginine at position 89 in the B-chain with another amino acid; (II) replacement of threonine at position 69 or serine at position 22 in the B-chain with another amino acid; (III) replacement of alanine at position 200 in the B-chain with another amino acid; and (IV) replacement of lysine at position 65 in the B-chain with threonine.Type: ApplicationFiled: November 15, 2007Publication date: February 18, 2010Applicants: Chisso Corporation, Fujimori Kogyo Co., Ltd.Inventors: Kazuyu Hosokawa, Tomoko Wada
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Publication number: 20100021934Abstract: A method for the detection in a body fluid of perlecan polypeptide fragments that are biomarkers of tumor metastasis, and antibodies for detecting these fragments are described. An immunoassay kit for detecting the presence of these biomarkers in a body fluid, such as serum or urine, is also described.Type: ApplicationFiled: June 16, 2009Publication date: January 28, 2010Applicant: University of DelawareInventor: Mary C. Farach-Carson
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Publication number: 20090258004Abstract: The invention is directed to blood proteins produced in monocot seeds and isolated therefrom for use in therapeutic compositions, and to methods of making these isolated blood proteins and to therapeutic compositions comprising them.Type: ApplicationFiled: November 27, 2007Publication date: October 15, 2009Inventors: Ning Huang, Raymond L. Rodriquez, Frank E. Hagie, David M. Stalker
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Publication number: 20090186395Abstract: A method for purifying a protein solution from infective particles comprising (a) adding a macromolecule to the solution; and (b) passing the solution through a nanofilter. The macromolecule may be selected from a polymer of at least 3 monomers of sugars, amino acids, glycols, alcohols, lipids or phospholipids.Type: ApplicationFiled: June 25, 2007Publication date: July 23, 2009Inventors: Israel Nur, Roni Mintz
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Publication number: 20090137001Abstract: The present invention provides for a process for preparing a recombinant human thrombin. A process for preparing a recombinant human thrombin which comprises: (1) obtaining a transfectant cell producing a human prothrombin by introducing an expression vector, wherein a gene fragment coding for a human prothrombin gene is incorporated, into an animal cell; (2) purifying a human prothrombin from the culture of the transfectant cell above by an anion exchanger; (3) converting the purified human prothrombin into a human thrombin by subjecting said human prothrombin to the action of ecarin; and (4) purifying the human thrombin from the solution after treatment with ecarin by an affinity method using benzamidine and a cation exchanger, and human thrombin obtained by said process, and a CHO cell that produces human prothrombin.Type: ApplicationFiled: September 29, 2006Publication date: May 28, 2009Inventors: Tatsufumi Onchi, Yo Nakahara, Takayuki Imamura, Toshinobu Nouchi, Hiroshi Nakatake
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Publication number: 20090105116Abstract: There is provided herein a multivalent binding molecule and uses thereof. The molecule is useful in binding a target under certain conditions and releasing it under other conditions. The molecule has the general formula (1) of BM1-L-(BM2)n (1) wherein, BM1 is a binding moiety 1 having an affinity for site 1 on the target, BM2 is a binding moiety 2 having an affinity for a site other than site 1 on the target, n is 1 or greater, and L is a linker joining BM1 and BM2, said linker being adapted to respond to a change in its environment with a change in conformation and/or flexibility, wherein BM1 and BM2 may be the same or different and are selected such that in use each of the BM1 and BM2 existing separately has a lower binding affinity then the complex of BM1 and BM2 does when they are linked to form the molecule. BM2 may have a single binding region or multiple binding regions with affinity for the target.Type: ApplicationFiled: June 20, 2005Publication date: April 23, 2009Inventors: Feng Ni, Dmitri Tolkatchev, Zhengding Su
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Patent number: 7494971Abstract: The invention relates to a pharmaceutical active ingredient preparation for producing a medicament that contains thrombin or has a thrombin-generating capacity and compositions comprising thereof. The inventive preparation contains: (A) prothrombin obtained from plasma or by means of genetic engineering (coagulation factor II), (B) coagulation factors V, VIII, IX, X obtained from plasma or by means of genetic engineering, which can be at least partially in the activated state, and coagulation factor Xla obtained from plasma or by means of genetic engineering, and (C) phospholipids which are safe from prions and contribute to the clotting process, said phospholipids being optionally contained in liposomes.Type: GrantFiled: January 21, 2005Date of Patent: February 24, 2009Assignee: Bio & Bio Licensing SAInventor: Johann Eibl
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Publication number: 20090047273Abstract: The present invention relates to a method is provided for producing recombinant human thrombin from recombinant prothrombin using recombinant ecarin having the sequence SEQ ID NO 2 or a homologue thereof.Type: ApplicationFiled: July 3, 2008Publication date: February 19, 2009Inventors: Anna Harrysson, Ann Lovgren
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Publication number: 20090042218Abstract: The present invention relates to a labeling enzyme and a method of detecting and/or quantifying a target substance using this labeling enzyme. The present invention provides a labeling enzyme that catalyzes a reaction of gelling a substrate. By measuring changes in physical properties such as the film thickness and/or refractive index of a film produced by the gelling reaction catalyzed by the labeling enzyme of the present invention, it is possible to quickly and highly sensitively detect and/or quantify a target substance while minimizing the effects of coexisting substances.Type: ApplicationFiled: September 21, 2005Publication date: February 12, 2009Inventors: Kazunori Ikebukuro, Koji Sode, Akira Umezawa, Kyoko Umezawa, Hironobu Yamamoto
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Patent number: 7473543Abstract: Compositions comprising thrombin and methods of preparing them are disclosed. The composition may be in the form of an aqueous solution at pH 5.7-7.4 consisting essentially of 0.1 mg/mL to 5.0 mg/mL thrombin, 2% to 4% (w/v) sucrose, 3.5% to 5% (w/v) mannitol, 50 mM to 300 mM NaCl, 0-5 mM CaCl2, 0.03% to 1% (w/v) of a surfactant or high-molecular-weight polyethylene glycol, and a physiologically acceptable buffer, or may be in lyophilized form.Type: GrantFiled: October 6, 2006Date of Patent: January 6, 2009Assignee: ZymoGenetics, Inc.Inventors: Shan Jiang, Richard I. Senderoff, Jeffrey D. Meyer
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Publication number: 20080293122Abstract: Methods for converting prethrombin-1 to thrombin are disclosed. An aqueous solution of prethrombin-1 is applied to oscutarin-C immobilized on a solid support so as to provide from 500 mg to 4000 mg of prethrombin-1 per mL of the solid support and a contact time between the prethrombin-1 and the oscutarin-C of from 1.8 to 3.5 minutes. The resulting active thrombin may be captured on an ion exchange chromatography medium or an affinity chromatography medium.Type: ApplicationFiled: December 21, 2006Publication date: November 27, 2008Inventors: Robert W. Mallet, Christopher J. Stenland, Jonathon C. Boone, John W. Forstrom, Karen S. De Jongh
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Publication number: 20080280343Abstract: The invention relates to thrombin compositions with reduced levels of high molecular weight impurities. In particular, the levels of factor Va, prions and/or viral agents are greatly reduced. This invention also relates generally to methods for the preparation of thrombin having a high degree of purity and high specific activity. More specifically, the invention encompasses steps to exclude high molecular weight impurities from thrombin preparations by size exclusion filtration. In additional embodiments, the preparation of thrombin additionally includes an ion exchange filtration step. The methods of the invention are particularly suited for large scale purification of thrombin. This invention also relates generally to stabilized formulations containing thrombin compositions. More specifically, the present invention relates to stabilized, liquid formulations containing thrombin having a high degree of purity and high specific activity and methods of making and using such formulations.Type: ApplicationFiled: October 30, 2007Publication date: November 13, 2008Inventors: Dan Pawlak, Bradley H. Knoll, Abdel Hak Terrab, Gerald Chesmore, J. Foster Irwin
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Publication number: 20080274532Abstract: The present invention provides a blood coagulation accelerator excellent under severe conditions at ordinary or higher temperatures and capable of exhibiting high blood coagulation performance stably over a long period of time, as well as a container for blood examination wherein the blood coagulation accelerator is accommodated. Disclosed is a blood coagulation accelerator comprising an enzyme capable of hydrolyzing in a peptide chain a bond between arginine and an arbitrary amino acid residue and/or a bond between lysine and an arbitrary amino acid residue, an inactivated enzyme product comprising the above-mentioned enzyme inactivated by radiation irradiation, and ?-alanine.Type: ApplicationFiled: March 15, 2006Publication date: November 6, 2008Inventors: Masaaki Minamoto, Kazuhiko Shimada
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Publication number: 20080254446Abstract: An aptamer-probe complex for detecting the presence of a target molecule is disclosed. The complex of the present invention contains an aptamer moiety which is able to bind to an indicator protein and change the properties of the indicator protein, and a probe moiety which is able to bind to a target molecule, wherein the aptamer moiety and the probe moiety are combined in such a manner that the binding mode between the aptamer moiety and the indicator protein changes when the probe moiety binds to the target molecule. A target molecule can be detected with combination of an aptamer which binds to a certain protein, and a probe which binds to the target molecule, utilizing the properties of that protein as an indicator.Type: ApplicationFiled: November 22, 2004Publication date: October 16, 2008Applicant: Techno Medica Co., LtdInventors: Koji Sode, Kazunori Ikebukuro
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Publication number: 20080254019Abstract: This invention provides therapeutic agents, transplants and therapeutic methods that can enhance the regeneration of injured tissue. This invention relates to agents, transplants and therapeutic methods for enhancing the migration and accumulation of mesenchymal stem cells in injured tissues and/or suppressing the diffusion of mesenchymal stem cells from injured tissues.Type: ApplicationFiled: March 31, 2005Publication date: October 16, 2008Inventors: Yukio Kato, Masahiro Nishimura, Yoshie Ozaki, Koichiro Tsuji
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Publication number: 20080219998Abstract: The present invention embodies: methods; compounds, their pharmaceutically acceptable analogs, isomer, salts, hydrates, solvates and prodrug derivatives, and pharmaceutically acceptable compositions thereof that have particular biological properties; devices; diagnostic and other assays; and the uses of such methods, compounds, devices and assays. Common throughout these embodiments is specific selective reduction of intravascular thromboplastin antecedent activity, which results in a safe antithrombotic effect. A particularly prominent application or the invention relates to diagnosis and treatment of patients which have, or are at risk of, developing thrombosis, thrombotic injury, or vaso-occlusive diseases, such as myocardial infarction, stroke, restenosis after angioplasty, thrombotic diseases, etc. Another particularly prominent feature of the present invention is its high level of hemostatic safety at optimal efficacy.Type: ApplicationFiled: May 8, 2002Publication date: September 11, 2008Inventor: Andras Gruber
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Patent number: 7393674Abstract: Compositions comprising thrombin and methods of preparing them are disclosed. The composition may be in the form of an aqueous solution at pH 5.7-7.4 consisting essentially of 0.1 mg/mL to 5.0 mg/mL thrombin, 2% to 4% (w/v) sucrose, 3.5% to 5% (w/v) mannitol, 50 mM to 300 mM NaCl, 0-5 mM CaCl2, 0.03% to 1% (w/v) of a surfactant or high-molecular-weight polyethylene glycol, and a physiologically acceptable buffer, or may be in lyophilized form.Type: GrantFiled: June 21, 2005Date of Patent: July 1, 2008Assignee: Zymogenetics, Inc.Inventors: Shan Jiang, Richard I. Senderoff, Jeffrey D. Meyer
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Patent number: 7371722Abstract: The invention relates to a pharmaceutically active substance for producing a drug that is capable of generating thrombin or that contains thrombin and compositions comprising thereof. The pharmaceutically active substance contains (A) prothrombin (coagulation factor II) obtained from plasma or by genetic engineering, (B) coagulation factors V, VIII, IX, X obtained from plasma or by genetic engineering that at least partially may be present in their activated state, and coagulation factor XIa obtained from plasma or by genetic engineering, and (C) prion-safe, coagulation-promoting phospholipids, where the phospholipids are optionally contained in liposomes.Type: GrantFiled: January 21, 2005Date of Patent: May 13, 2008Assignee: Bio & Bio Licensing S.A.Inventor: Johann Eibl
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Patent number: 7354905Abstract: There is provided compounds of formula I, R1O(O)C—CH2—(R)Cgl-Aze-Pab-R2I wherein R1 and R2 have meanings given in the description, which are useful as prodrugs of inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required (eg thrombosis) or as anticoagulants.Type: GrantFiled: February 12, 2004Date of Patent: April 8, 2008Assignee: AstraZeneca ABInventors: Thomas Antonsson, David Gustafsson, Kurt-Jürgen Hoffmann, Jan-Erik Nyström, Henrik Sörensen, Mikael Sellén
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Patent number: 7060484Abstract: Novel polypeptides (NPs) are provided which are capable of protein C activation without significant fibrinogen clotting activity, and vice versa. NPs having enhanced protein C activating properties in relation to fibrinogen clotting are useful in particular as anticoagulants and in screening for substances that agonize or antagonize this property and in diagnostic procedures to determine the status of patients' activated protein C-mediated anticoagulant pathway. Procoagulant NPs are useful to promote clotting in the course of therapy of solid tumors, as an impregnate for bandages, or in diagnostic assays. The NPs are produced in recombinant cell culture or by in vitro methods.Type: GrantFiled: February 16, 2000Date of Patent: June 13, 2006Assignee: Gilead Sciences, Inc.Inventors: Craig S. Gibbs, Lawrence L. K. Leung, Manuel Tsiang
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Patent number: 7056722Abstract: A sterile method for preparing stable thrombin component from a single donor's plasma in which the thrombin component is harvested simultaneously from the clotting and adhesive proteins component from the same donor plasma in less than one hour. The combined components provide an improved biological hemostatic agent and tissue sealant by virtue of its freedom from the risk of contaminating viruses or bacteria from allogenic human or bovine blood sources. The thrombin provides polymerization of the clotting and adhesive proteins in less than five seconds, and is sufficiently stable to provide that fast clotting over a six hour period. Further, the clotting times can be predictably lengthened by diluting the thrombin with saline.Type: GrantFiled: November 10, 2000Date of Patent: June 6, 2006Assignee: ThermoGenesis Corp.Inventors: Philip Henry Coelho, Phil Kingsley, Jim Brausch, James H. Godsey, Gail Rock
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Methods and compositions for treating platelet-related disorders using MPL pathway inhibitory agents
Patent number: 7022521Abstract: The invention relates to the treatment of subjects for the purpose inhibiting vaso-occlusive events, including thrombosis and embolism, by administering agents which reduce the number of circulating platelets to low or below normal levels. Methods and pharmaceutical preparations comprising such agents are provided.Type: GrantFiled: June 24, 2003Date of Patent: April 4, 2006Assignee: Emory UniversityInventor: Stephen R. Hanson -
Patent number: 7005271Abstract: The present invention relates to determining the prethrombotic state, in particular determining an amount or presence of circulating microparticles and/or stimulated procoagulant cells.Type: GrantFiled: June 7, 2000Date of Patent: February 28, 2006Inventors: Jean-Marie Freyssinet, Benedicte Antoni, Frederic Donie, Helmut Lill
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Patent number: 6946279Abstract: A thrombin derivative having a lowered fibrinogen activity, a process for producing thereof, an anhydrothrombin derivative having a lowered fibrinogen activity, and a process for producing thereof are provided. This invention is to provide a thrombin derivative formed by modifying carboxyl group(s) of the thrombin and an anhydrothrombin derivative formed by modifying carboxyl group(s) of the anhydrothrombin. The thrombin derivative can be utilized as a composition for inducing platelet aggregation and further as a reagent of specific aggregation for clinical testing and the like. By affinity chromatography using carboxyl group(s) bound with anhydrothrombin as a ligand, it is made possible to carry out necessary purification with high selectivity relative to the blood coagulation factor VIII.Type: GrantFiled: March 19, 2002Date of Patent: September 20, 2005Assignees: Fujimori Kogyo Co., Ltd., Chisso CorporationInventor: Kazuya Hosokawa
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Patent number: 6936430Abstract: Method of detecting coagulation abnormalities in a plasma sample by (a) determining a test rate of thrombin generation over a given time interval by reacting an activator of thrombin with defibrinated normal plasma in the presence of a defibrinated test plasma sample; (b) determining a control rate of thrombin generation over substantially the same time interval in step (a) by reacting the same activator of thrombin with defibrinated normal plasma in the absence of any defibrinated test plasma; and (c) comparing the rates of thrombin generation between test step (a) and control step (b) such that any significant difference between the two thrombin generation rates being indicative of a coagulation abnormality in the test plasma.Type: GrantFiled: April 12, 2000Date of Patent: August 30, 2005Assignee: South Eastern Sydney Area Health ServiceInventor: Steven Krilis
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Patent number: 6869790Abstract: The cDNA which codes for factor XIIIa has been isolated using a cDNA bank from human placenta and probes constructed on the basis of the amino acid sequence of factor XIIIa peptide fragments. It is possible with this cDNA not only to obtain factor XIIIa by gene manipulation in high purity but also to prepare diagnostic aids which permit the analysis of genetic factor XIIIa defects. Furthermore, it is possible on the basis of the amino acid sequence to prepare antibodies which are suitable for diagnostic aids and antibody columns.Type: GrantFiled: March 12, 1993Date of Patent: March 22, 2005Assignee: Aventis Behring GmbHInventors: Ulrich Grundmann, Egon Amann, Gerd Zettlmeissl
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Patent number: 6846656Abstract: The present invention provides a process for economically producing N-acetylneuraminic acid without using expensive materials such as pyruvic acid and phosphoenolpyruvic acid. The process comprises: allowing (i) a culture of a microorganism having N-acetylneuraminic acid aldolase activity or N-acetylneuraminic acid synthetase activity, or a treated matter of the culture, (ii) a culture of a microorganism capable of producing pyruvic acid or a treated matter of the culture, or a culture of a microorganism capable of producing phosphoenolpyruvic acid or a treated matter of the culture, (iii) N-acetylmannosamine, and (iv) an energy source which is necessary for the formation of pyruvic acid or phosphoenolpyruvic acid to be present in an aqueous medium to form and accumulate N-acetylneuraminic acid in the aqueous medium; and recovering N-acetylneuraminic acid from the aqueous medium.Type: GrantFiled: August 25, 2000Date of Patent: January 25, 2005Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Satoshi Koizumi, Kazuhiko Tabata, Tetsuo Endo, Akio Ozaki
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Patent number: 6841354Abstract: A method for screening for anti-thrombotic/anti-platelet agents is provided where the method is based on inhibition of the GP Ib, PAR-1 and/or PAR-4 pathways by the potential anti-thrombotic/anti-platelet agent.Type: GrantFiled: December 21, 2001Date of Patent: January 11, 2005Assignee: Philadelphia, Health & Education CorporationInventor: Gerald Soslau
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Publication number: 20040229333Abstract: The invention is directed to formation and use of electroprocessed fibrin as an extracellular matrix and, together with cells, its use in forming engineered tissue. The engineered tissue can include the synthetic manufacture of specific organs or tissues which may be implanted into a recipient. The electroprocessed fibrin may also be combined with other molecules in order to deliver the molecules to the site of application or implantation of the electroprocessed fibrin. The fibrin or fibrin/cell suspension is electrodeposited onto a substrate to form the tissues and organs.Type: ApplicationFiled: January 26, 2004Publication date: November 18, 2004Inventors: Gary L. Bowlin, Gary E. Wnek, David G. Simpson, Philippe Lam, Marcus E. Carr
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Publication number: 20040213777Abstract: Provided are methods of applying biological compositions, that is, autologous bioadhesive sealant compositions containing one or more biological agents, to an individual, wherein all the blood components used in preparing the composition are derived from the patient who is to receive the biological composition. In one embodiment, the method comprises obtaining a whole blood sample from an individual; forming an inactive platelet rich plasma from the whole blood sample; mixing a biological agent into the inactive platelet rich plasma; obtaining thrombin from the whole blood sample; mixing the thrombin into the inactive platelet rich plasma to form a biological composition; and applying the biological composition to the individual.Type: ApplicationFiled: May 18, 2004Publication date: October 28, 2004Inventors: Robert F. Baugh, Lisa M. Lim, Julie S. Johnston, John G. Rivera
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Publication number: 20040214280Abstract: Novel polypeptides (NPs) are provided which are capable of protein C activation without significant fibrinogen clotting activity, and vice versa. NPs having enhanced protein C activating properties in relation to fibrinogen clotting are useful in particular as anticoagulants and in screening for substances that agonize or antagonize this property and in diagnostic procedures to determine the status of patients' activated protein C-mediated anticoagulant pathway. Procoagulant NPs are useful to promote clotting in the course of therapy of solid tumors, as an impregnate for bandages, or in diagnostic assays. The NPs are produced in recombinant cell culture or by in vitro methods.Type: ApplicationFiled: January 20, 2004Publication date: October 28, 2004Applicant: Gilead Sciences, Inc.Inventors: Craig S. Gibbs, Lawrence L.K. Leung, Manuel Tsiang
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Publication number: 20040197858Abstract: A genetic recombinant human thrombin is provided. Human thrombin is efficiently prepared by the genetic engineering technique comprising the steps: (1) culturing a transfectant animal cell transfected with an expression vector in which a gene encoding human prethrombin is incorporated to the downstream of a promoter so as to produce and accumulate prethrombin in culture supernatant and recovering the produced human prethrombin; (2) treating a solution containing human prethrombin recovered in step (1) with ecarin so as to convert human prethrombin into human thrombin; and (3) purifying the solution obtained after the above activation process to obtain purified human thrombin. The present invention allows for provision of human thrombin in a large scale in a safe and economical manner due to exclusion of blood-derived components.Type: ApplicationFiled: January 6, 2004Publication date: October 7, 2004Inventors: Hiroshi Yonemura, Takayuki Imamura, Hiroshi Nakatake, Kenji Soejima, Chikateru Nozaki
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Publication number: 20040120943Abstract: The present invention relates to novel antithrombotic variants of thrombin or fragments thereof that are capable of proteolytically activating protein C, but which are substantially free of fibrinogen cleavage activity. The present invention further relates to variant polypeptidess that may be cleaved to yield active thrombin variants. The present invention also relates to methods of inhibiting thrombus formation in an animal or human subject by delivering an antithrombotic variant thrombin of the present invention to the blood of the subject. The present invention relates also to methods that use the novel variant thrombins for determining the level of protein C activation in a blood sample, or the thrombogenic potential of a patient.Type: ApplicationFiled: October 31, 2003Publication date: June 24, 2004Applicant: Emory UniversityInventors: Andras Gruber, Stephen R. Hanson, Enrico Di Cera
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Publication number: 20040096953Abstract: A thrombin derivative having a lowered fibrinogen activity, a process for producing thereof, an anhydrothrombin derivative having a lowered fibrinogen activity, and a process for producing thereof are provided. This invention is to provide a thrombin derivative formed by modifying carboxyl group(s) of the thrombin and an anhydrothrombin derivative formed by modifying carboxyl group(s) of the anhydrothrombin. The thrombin derivative can be utilized as a composition for inducing platelet aggregation and further as a reagent of specific aggregation for clinical testing and the like. By the affinity chromatography having carboxyl group(s) bound with anhydrothrombin as a ligand, it is made possible to carry out necessary purification with high selectivity relative to the blood coagulation factor VIII.Type: ApplicationFiled: November 21, 2003Publication date: May 20, 2004Inventor: Kazuya Hosokawa
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Patent number: 6706512Abstract: The present invention relates to novel antithrombotic variants of thrombin or fragments thereof that are capable of proteolytically activating protein C, but which are substantially free of fibrinogen cleavage activity. The present invention further relates to variant polypeptidess that may be cleaved to yield active thrombin variants. The present invention also relates to methods of inhibiting thrombus formation in an animal or human subject by delivering an antithrombotic variant thrombin of the present invention to the blood of the subject. The present invention relates also to methods that use the novel variant thrombins for determining the level of protein C activation in a blood sample, or the thrombogenic potential of a patient.Type: GrantFiled: June 7, 2002Date of Patent: March 16, 2004Assignee: Emory UniversityInventors: Andras Gruber, Stephen R. Hanson, Enrico De Cera
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Patent number: 6683054Abstract: According to the invention there is provided the use of melagatran, or a pharmaceutically acceptable derivative or prodrug thereof, in the manufacture of a medicament for the treatment of inflammation.Type: GrantFiled: March 16, 2000Date of Patent: January 27, 2004Assignee: AstraZeneca ABInventor: Ian Kirk