Antithrombin Iii Patents (Class 530/393)
  • Publication number: 20150147345
    Abstract: This document relates to conjugates of a biologically active molecule or a derivative thereof and functionalized (e.g., mono- or bi-functional) polymers (e.g., polyethylene glycol and related polymers) as well as methods and materials for making and using such conjugates.
    Type: Application
    Filed: June 12, 2013
    Publication date: May 28, 2015
    Inventor: Marek Kwiatkowski
  • Patent number: 8822654
    Abstract: The present invention relates to the use of a composition including of at least a mutated antithrombin having an anticoagulant activity substantially reduced with respect to the anticoagulant activity of the non mutated antithrombin, or having no anticoagulant activity, for the preparation of a drug intended for the prevention or the treatment of pathologies associated with cellular injury, such as infection, inflammation or hypoxic injury.
    Type: Grant
    Filed: January 15, 2010
    Date of Patent: September 2, 2014
    Assignees: Universite Paris—Sud XI, Assistance Publique-Hopitaux de Paris, Universite Paris Descartes
    Inventors: Delphine Borgel, Véronique Ferger, Elsa Bianchini, Nicolas Lerolle, Jean-Luc René Diehl
  • Publication number: 20140242182
    Abstract: In one aspect, the disclosure provides formulations that stabilize proteins, wherein the formulations comprise a buffer. In some embodiments, the buffer comprises potassium mono-hydrogen-phosphate and potassium di-hydrogen-phosphate, or the buffer comprises sodium mono-hydrogen-phosphate and sodium di-hydrogen-phosphate. In some embodiments, the protein is a therapeutic protein. In some embodiments, the therapeutic protein is antithrombin.
    Type: Application
    Filed: July 6, 2012
    Publication date: August 28, 2014
    Applicant: rEVO Biologics, Inc
    Inventors: Sean A. Evans, Greg J. Allard, Nicholas C. Masiello
  • Publication number: 20140148585
    Abstract: The present invention relates to protein purification. More particularly, a method for directly recovering an objective protein from a protein composition and purifying a protein with a desired quality in a rapid and efficient manner is provided. Further, a rapid purification method capable of efficiently removing impurities included in the protein composition is provided. Therefore, compared to the conventional purification methods, quality and yield of the protein can be remarkably improved.
    Type: Application
    Filed: June 28, 2012
    Publication date: May 29, 2014
    Applicant: KYOWA HAKKO KIRIN CO., LTD
    Inventors: Tsutomu Sugihara, Tomoko Isoda, Yuya Taniguchi, Hidetaka Nomura, Toshiyuki Suzawa
  • Patent number: 8648177
    Abstract: Method for lyophilization is provided, in particular methods for lyophilization of formulations comprising AT III. Also provided are compositions prepared by therefrom. Also provided are kits comprising the compositions and/or lyophilized products.
    Type: Grant
    Filed: November 23, 2010
    Date of Patent: February 11, 2014
    Assignee: Grifols Therapeutics Inc.
    Inventors: Jianxin Guo, Anthony Klos, Deborah Barnette
  • Patent number: 8618266
    Abstract: The present invention relates to hydroxyalkylstarch (HAS)-polypeptide-conjugate (HAS-polypeptide) comprising one or more HAS molecules, wherein each HAS is conjugated to the polypeptide via a carbohydrate moiety or a thioether as well as to methods for the production thereof. In a preferred embodiment, the polypeptide is erythropoietin (EPO).
    Type: Grant
    Filed: March 11, 2005
    Date of Patent: December 31, 2013
    Assignee: Fresenius Kabi Deutschland GmbH
    Inventors: Harald S. Conradt, Eckart Grabenhorst, Manfred Nimtz, Norbert Zander, Ronald Frank, Wolfram Eichner
  • Patent number: 8216788
    Abstract: The present disclosure relates to methods and compositions for the detection of infectious proteins or prions in samples, including the diagnosis of prion related diseases. One embodiment is an ultrasensitive method for detecting PrP-res (PrPSc) that allows the use of recombinant PrP-sen (rPrP-sen) as a substrate for seeded polymerization. A sample is mixed with purified rPrP-sen to make a reaction mix which is incubated to permit aggregation of the rPrP-sen with the PrP-res that may be present in the sample. Any aggregates are intermittently disaggregated by agitation (for example by sonication) and the reaction allowed to proceed to amplify target substrate. Any rPrP-res(Sc) in the reaction mix is detected to indicate the presence of PrP-res in the original sample. This assay, which is called rPrP-PMCA, is surprisingly much faster than existing PMCA methods, yet it still retains sufficient sensitivity to detect extremely low levels of PrP-res.
    Type: Grant
    Filed: July 21, 2008
    Date of Patent: July 10, 2012
    Assignee: The United States of America as represented by the Secretary of the Department of Health and Human Services
    Inventors: Byron W. Caughey, Ryuichiro Atarashi, Roger A. Moore
  • Publication number: 20120135931
    Abstract: The present invention relates to a method of modifying serine protease inhibitors in order to acquire or enhance any one of a variety of desired properties, including extent of inhibition, maintenance of inhibition following cleavage of the serine protease inhibitor by the target serine protease, speed of binding to the serine protease, neutralisation, and binding affinity. The present invention also relates to the products of such modifications and the uses of such products, in particular, their use in therapy.
    Type: Application
    Filed: May 5, 2010
    Publication date: May 31, 2012
    Applicant: NATURAL ENVIRONMENT RESEARCH COUNCIL
    Inventors: R. Manjunatha Kini, Cho Yeow Koh, Kunchithapadam Swaminathan, Kumar Sundramurthy
  • Publication number: 20120088715
    Abstract: The present invention relates to the use of a composition including of at least a mutated antithrombin having an anticoagulant activity substantially reduced with respect to the anticoagulant activity of the non mutated antithrombin, or having no anticoagulant activity, for the preparation of a drug intended for the prevention or the treatment of pathologies associated with cellular injury, such as infection, inflammation or hypoxic injury.
    Type: Application
    Filed: January 15, 2010
    Publication date: April 12, 2012
    Applicants: UNIVERSITE PARIS-SUD XI, UNIVERSITE PARIS DESCARTES, ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS
    Inventors: Delphine Borgel born Botbol, Veronique Ferger born Picard, Elsa Bianchini, Nicolas Lerolle, Rene Jean-Luc Diehl
  • Patent number: 8084580
    Abstract: The invention discloses a purified albumin solution of human origin with low prekallicrein activator (PKA) activity and stability over time characterized in that it has an antithrombin content equal to or greater than 0.03 mg/g of albumin, and a process for production thereof by the partial extraction of the antithrombin during fractionation of the human plasma.
    Type: Grant
    Filed: March 21, 2007
    Date of Patent: December 27, 2011
    Assignee: Grifols, S.A.
    Inventors: Juan Ignacio Jorquera Nieto, Nuria Hosta Mateu, Olga Santaeularia Lozano
  • Patent number: 8076462
    Abstract: The provision of an antithrombin composition having a desired ?-form content rate or ?-form content rate is required. The invention provides a process for producing an antithrombin composition having a desired ?-form content rate or ?-form content rate which is prepared by contacting an antithrombin-containing aqueous solution with a Cellufine Sulfate chromatography carrier.
    Type: Grant
    Filed: April 2, 2008
    Date of Patent: December 13, 2011
    Assignee: Kyowa Hakko Kirin Co., Ltd
    Inventors: Tsutomu Sugihara, Setsuko Onodera, Tomonari Urakubo, Toshiyuki Suzawa
  • Publication number: 20110195478
    Abstract: The present invention discloses a bladder cancer biomarker and a test method using the same. The biomarker contains at least one of the mentioned 69 compounds, such as apolipoprotein A1 (APOA1), apolipoprotein A2 (APOA2), peroxiredoxin 2 (PRDX2), heparin cofactor 2 precursor (HCII), and serum amyloid A-4 protein (SAA4), which exist in the urine specimen of a testee. The expression intensity of the biomarker can facilitate diagnosis of bladder cancer and evaluation of aggressiveness and malignancy of bladder cancer. Thereby, the physician can arrange an optimized treatment to achieve the best therapeutic effect.
    Type: Application
    Filed: August 4, 2010
    Publication date: August 11, 2011
    Inventors: Yi-Ting Chen, Jau-Song Yu, Chien-Lun Chen, Yu-Sun Chang
  • Patent number: 7928064
    Abstract: This invention relates to transgenically produced human Antithrombin III (tgATIII). The human ATIII produced by the transgenic process of the present invention has a monosaccharide composition which comprises N-acetylgalactosamine (GalNAc) along with fucose, N-acetylglucosamine, galactose, mannose, and N-acetylneuraminic acid/N-glycolyneuraminic acid. The monosaccharide composition differs with that of plasma derived ATIII (phATIII). It has been found that tgATIII has an increased clearance rate when compared to phATIII.
    Type: Grant
    Filed: November 14, 2005
    Date of Patent: April 19, 2011
    Assignee: GTC Biotherapeutics, Inc.
    Inventors: Paul DiTullio, Harry M. Meade, Edward S. Cole
  • Patent number: 7923217
    Abstract: Methods and reagents for determining antithrombin III (AT) in body fluids by adding an AT binding partner to the sample and determining the free AT binding partner.
    Type: Grant
    Filed: August 29, 2003
    Date of Patent: April 12, 2011
    Assignee: Roche Diagnostics Operations, Inc.
    Inventor: Adena Enno
  • Publication number: 20110053214
    Abstract: The present invention provides a novel lower eukaryotic host cell producing human-like glycoproteins characterized as having a terminal ?-galactose residue and essentially lacking fucose and sialic acid residues. The present invention also provides a method for catalyzing the transfer of a galactose residue from UDP-galactose onto an acceptor substrate in a recombinant lower eukaryotic host cell, which can be used as a therapeutic glycoprotein.
    Type: Application
    Filed: July 21, 2010
    Publication date: March 3, 2011
    Applicant: GLYCOFI, INC.
    Inventors: Robert Collier Davidson, Tillman Ulf Gerngross, Stefan Wildt, Byung-Kwon Choi, Juergen Hermann Nett, Piotr Bobrowicz, Stephen Robin Hamilton
  • Publication number: 20100183589
    Abstract: 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: Application
    Filed: March 31, 2010
    Publication date: July 22, 2010
    Applicant: VENTRIA BIOSCIENCE
    Inventors: Ning Huang, Raymond L. Rodriguez, Frank E. Hagie, David M. Stalker
  • Publication number: 20100113754
    Abstract: The provision of an antithrombin composition having a desired ?-form content rate or ?-form content rate is required. The invention provides a process for producing an antithrombin composition having a desired ?-form content rate or ?-form content rate which is prepared by contacting an antithrombin-containing aqueous solution with a Cellufine Sulfate chromatography carrier.
    Type: Application
    Filed: April 2, 2008
    Publication date: May 6, 2010
    Applicant: KYOWA HAKKO KIRIN CO., LTD.
    Inventors: Tsutomu Sugihara, Setsuko Onodera, Tomonari Urakubo, Toshiyuki Suzawa
  • Patent number: 7691810
    Abstract: The present invention provides a process for producing an antithrombin III composition comprising an antithrombin III molecule having complex type N-glycoside-linked sugar chains, wherein the complex type N-glycoside-linked sugar chains have a structure in which fucose is not bound to N-acetylglucosamine in the reducing end in the sugar chains.
    Type: Grant
    Filed: October 7, 2004
    Date of Patent: April 6, 2010
    Assignee: Kyowa Hakko Kirin Co., Ltd
    Inventors: Tsuyoshi Yamada, Mitsuo Satoh, Yutaka Kanda, Kazuya Yamano
  • Publication number: 20090258004
    Abstract: 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: Application
    Filed: November 27, 2007
    Publication date: October 15, 2009
    Inventors: Ning Huang, Raymond L. Rodriquez, Frank E. Hagie, David M. Stalker
  • Patent number: 7332577
    Abstract: The invention discloses a purified albumin solution of human origin with low prekallicrein activator (PKA) activity and stability over time characterised in that it has an antithrombin content equal to or greater than 0.03 mg/g of albumin, and a process for production thereof by the partial extraction of the antithrombin during fractionation of the human plasma.
    Type: Grant
    Filed: July 19, 2005
    Date of Patent: February 19, 2008
    Assignee: Grifols, S.A.
    Inventors: Juan Ignacio Jorquera Nieto, Olga Santaeularia Lozano, Nuria Hosta Mateu
  • Patent number: 7001993
    Abstract: Human antithrombin variants showing a high protease inhibitory activity even in the absence of heparin wherein at least one of the amino acids at positions 78, 278, 378 and 380 in the amino acid sequence of natural human antithrombin is substituted by another amino acid. Preferable examples thereof are human antithrombin variants wherein the amino acid at position 78 is substituted by Phe; the amino acid at position 278 is substituted by Ala, Arg, Asn, Gly, His, Tyr or Val; the amino acid at position 378 is substituted by Lys, Asn or Val; and/or the amino acid at position 380 is substituted by Ala, Asp, Gly, His, lie, Leu, Asn, Pro, Arg, Thr, Tyr or Val.
    Type: Grant
    Filed: June 22, 2000
    Date of Patent: February 21, 2006
    Assignee: Aventis Pharma Ltd.
    Inventor: Takehiko Koide
  • Patent number: 6878813
    Abstract: The present invention discloses modified antithrombin III compounds and methods. The amino acid compounds of the present invention are useful in treating blood clotting disorders, as well as other disease states associated with enzymes in the coagulation pathway.
    Type: Grant
    Filed: December 11, 2001
    Date of Patent: April 12, 2005
    Assignees: Temple University - of the Commonwealth System of Higher Education, University of Utah Research Foundation
    Inventors: Susan C. Bock, Veronique Picard, Pedram Zendehrouh
  • Patent number: 6777541
    Abstract: The present invention relates to a process for the preparation of a solution comprising a substantially pure isoform of AT-III, said process comprising separating the isoform AT-III&agr; from AT-III&bgr; on a calcium hydroxyphosphate-based adsorbent.
    Type: Grant
    Filed: January 19, 2001
    Date of Patent: August 17, 2004
    Assignee: Octapharma AG
    Inventor: Göran Karlsson
  • Patent number: 6518406
    Abstract: The present invention relates to methods for purification of antithrombin-III (AT-III) by precipitation of impurities. The said methods comprise (a) adding, to a solution comprising antithrombin-III, a saccharide and citrate, in an amount sufficient for impurities to precipitate while antithrombin-III essentially remains in solution; (b) allowing impurities to precipitate; and (c) removing the precipitated impurities, thereby obtaining a solution comprising purified antithrombin-III. The invention also relates to pharmaceutical compositions, obtainable by the said methods, comprising purified antithrombin-III, as well as to reconstituted pharmaceutical compositions essentially free from visible particles.
    Type: Grant
    Filed: June 21, 2000
    Date of Patent: February 11, 2003
    Assignee: Octapharma AG
    Inventor: Stefan Winge
  • Patent number: 6491965
    Abstract: Novel conjugates of glycosaminoglycans, particularly heparin and dermatan sulfate, and amine containing species and therapeutic uses thereof are described. In particular, mild methods of conjugating heparins to proteins, such as antithrombin III and heparin cofactor II, which provide covalent conjugates which retain maximal biological activity are described. Uses of these conjugates to prevent thrombogenesis, in particular in lung airways, such as found in infant and adult respiratory distress syndrome, and on surfaces in contact with blood are also described.
    Type: Grant
    Filed: December 17, 1996
    Date of Patent: December 10, 2002
    Assignee: Hamilton Civic Hospitals Research Development, Inc.
    Inventors: Leslie Berry, Maureen Andrew
  • Patent number: 6441145
    Abstract: This invention relates to transgenically produced human Antithrombin III (tgATIII). The human ATIII produced by the transgenic process of the present invention has a monosaccharide composition which comprises N-acetylgalactosamine (GaINAc) along with fucose, N-acetylglucosamine, galactose, mannose, and N-acetylneuraminic acid/N-glycolyneuraminic acid. The monosaccharide composition differs with that of plasma derived ATIII (phATIII). It has been found that tgATIII has an increased clearance rate when compared to phATIII.
    Type: Grant
    Filed: August 28, 1998
    Date of Patent: August 27, 2002
    Assignee: Genzyme Transgenics, Inc.
    Inventors: Paul DiTullio, Harry Meade, Edward S. Cole
  • Patent number: 6395880
    Abstract: A method of purifying antithrombin III (AT III) from a starting material containing an AT III/heparin complex or an AT III/heparinoid complex is disclosed. First, the method comprises adsorbing the AT III/heparin complex or the AT III/heparinoid complex on an anion exchanger material. Second, the method involves separating the AT III from the adsorbed AT III/heparin complex or an AT III/heparinoid complex by elution with a buffer having a pH ranging from 8.5 to 10.5 and a conductivity between 10 and 60 mS.
    Type: Grant
    Filed: May 26, 2000
    Date of Patent: May 28, 2002
    Assignee: Baxter Aktiengesellschaft
    Inventors: Yendra Linnau, Ernst Hetzl, H. Peter Matthiessen, Silvia Neppl, Wolfgang Schönhofer, Hans-Peter Schwarz
  • Patent number: 6395881
    Abstract: A process is disclosed for the baseline separation of the &agr; and &bgr; variants of antithrombin III AT-III. The process involves subjecting a sample comprising AT III to cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC). The CD-MEKC is performed with a buffer comprising boric acid, an anionic tensid, &bgr;-cyclodextrin, and an aliphatic diamine at a basic pH. The CD-MEKC results in the separation of the AT III into AT III &agr; and ATIII &bgr;. The anionic tensid can be sodium dodecyl sulfate and the aliphatic diamine can be 1, 5-diaminopentane.
    Type: Grant
    Filed: May 7, 2001
    Date of Patent: May 28, 2002
    Assignee: Aventis Behring GmbH
    Inventors: Reiner Doenges, Juergen Roemisch, Harald Stauss
  • Patent number: 6093804
    Abstract: The methods of the present invention provide a simple means for separating active and inactive Alpha Proteinase Inhibitor (API). The methods further provide means for purifying API at high yield (>70%), and at levels of purity (>90%) and activity (>90%) not heretofore available. Moreover, the methods of the present invention are simple (i.e., two chromatographic steps) and efficient; and are thus especially suitable to large scale purification processes. These methods will contribute substantially to alleviating the unmet demand for API for therapeutic purposes.
    Type: Grant
    Filed: September 24, 1998
    Date of Patent: July 25, 2000
    Assignee: American National Red Cross
    Inventors: Annemarie H. Ralston, William H. Drohan
  • Patent number: 5843705
    Abstract: This invention relates to transgenically produced human Antithrombin III (tgATIII). The human ATIII produced by the transgenic process of the present invention has a monosaccharide composition which comprises N-acetylgalactosamine (GaINAc) along with fucose, N-acetylglucosamine, galactose, mannose, and N-acetylneuraminic acid/N-glycolyneuraminic acid. The monosaccharide composition differs with that of plasma derived ATIII (phATIII). It has been found that tgATIII has an increased clearance rate when compared to phATIII.
    Type: Grant
    Filed: February 21, 1995
    Date of Patent: December 1, 1998
    Assignee: Genzyme Transgenic Corporation
    Inventors: Paul DiTullio, Harry Meade, Edward S. Cole
  • Patent number: 5817765
    Abstract: Virus inactivating chemicals and/or detergents in an aqueous composition containing a water-soluble plasma protein are reduced by selecting a suitable combination of temperature and concentration above 0.5M of salt with a high salting out effect according to the Hofmeister series, thereby forming vesicles containing the virus inactivating chemical and/or detergent. These vesicles are removed from the aqueous phase, e.g. by phase separation or filtration, and the protein thereafter isolated from the aqueous phase. The water-soluble plasma protein can be e.g. antithrombin III, transferrin or albumin. When the aqueous phase comprises e.g. a salt of citrate or sulphate in a concentration above 1M at room temperature, the reduction of virus inactivating chemical or detergent can be as high as 2000 times or more, giving a final concentration below 5 ppm.
    Type: Grant
    Filed: October 30, 1995
    Date of Patent: October 6, 1998
    Assignee: Pharmacia & Upjohn Aktiebolag
    Inventors: Sven Isaksson, Stefan Winge
  • Patent number: 5767108
    Abstract: A method of treating a patient with a medical device having immobilized heparin on a blood-contacting surface in which the covalently attached heparinized surface is provided with an adsorbed protein which may be activated by the immobilized heparin to block the coagulation of fibrinogen. Antithrombin III is the preferred adsorbed protein. The adsorbed protein is maintained on the immobilized heparin surface until the medical device is placed into contact with the patient's blood. When in contact with the patient's blood, the adsorbed protein will prevent initial thrombin formation at the biomaterial-blood interface. The preadsorption of ATIII is accomplished under conditions advantageous to maximum heparin/ATIII binding. When the preadsorbed surface comes in contact with whole blood, the maximum advantage of prophlactic properties of ATIII/heparin are obtained.
    Type: Grant
    Filed: August 22, 1995
    Date of Patent: June 16, 1998
    Assignee: Medtronic, Inc.
    Inventors: Patrick Cahalan, Theo Lindhout, Benedict Fouache, Michel Verhoeven, Linda Cahalan, Marc Hendriks, Ron Blezer
  • Patent number: 5589516
    Abstract: A liquid preparation of antithrombin-III (AT-III), comprising an AT-III and an organic acid, a salt thereof, a sugar sulfate or a surfactant as a stabilizer, and a liquid preparation of AT-III, having a pH of 9-10. The preparation of the present invention is stable after long-term preservation and poses no clinical problems in terms of pharmacological effects and safety. The preparation is more advantageous than lyophilized preparations in that it does not require dissolution in injectable distilled water and can be used easily. Accordingly, the preparation is clinically very useful.
    Type: Grant
    Filed: December 5, 1994
    Date of Patent: December 31, 1996
    Assignee: The Green Cross Corporation
    Inventors: Katsuhiro Uriyu, Akimasa Ohmizu, Hajime Fukuyama, Kazuo Takechi, Kazumasa Yokoyama
  • Patent number: 5439802
    Abstract: The present invention involves the determination of Protein S and Protein C activity in human plasma based on the addition of FIX.sub.a which indirectly influences the formation of thrombin.
    Type: Grant
    Filed: January 14, 1992
    Date of Patent: August 8, 1995
    Assignee: Chromogenix AB
    Inventor: Steffen Rosen
  • Patent number: 5420252
    Abstract: A novel human antithrombin III (AT III) mutant having a high antithrombin activity in the absence of heparin and effective in the treatment of thrombotic disorders as an anticoagulant, which is obtained by mutating amino acids at the reactive site and the heparin binding site of human AT III into another amino acids with the use of the recombinant DNA technology with the use of a DNA coding for AT III as a template. The invention also relates to a method for mass producing the above-described mutant by incubating a host transformed by an expression vector having the cDNA of the mutant inserted therein.
    Type: Grant
    Filed: April 9, 1993
    Date of Patent: May 30, 1995
    Assignee: Eisai Co., Ltd.
    Inventors: Hiroyuki Kato, Shinji Yoshitake, Suguru Suzuki, Noboru Suzuki, Toshio Seto, Naoko Nagaoka, Yoshiharu Mizui
  • Patent number: 5385890
    Abstract: An antithrombin III is described comprising a lyophilized powder of antithrombin III and a polyoxyethylene glycol sorbitan alkyl ester as well as a kit composed of a container wherein a lyophilized powder of antithrombin III is placed and a solvent for the powder, characterized in that a polyoxyethylene glycol sorbitan alkyl ester is added to either or both of the powder and the solvent. The preparation has a high solubility in water by retaining its activity.
    Type: Grant
    Filed: September 30, 1993
    Date of Patent: January 31, 1995
    Assignee: Hoechst Japan Limited
    Inventors: Toshinobu Aoyama, Keizo Hirahara
  • Patent number: 5319072
    Abstract: A method for purifying human antithrombin III in an alcoholic solution at low temperature using bound heparin is provided.
    Type: Grant
    Filed: January 10, 1992
    Date of Patent: June 7, 1994
    Assignee: Alpha Therapeutic Corporation
    Inventors: Yahiro Uemura, Swaraj Kaur, Prabir Bhattcharya
  • Patent number: 5252557
    Abstract: An antithrombin solution for preventing fibrin formations, including antithrombin at a concentration of more than 0.5 U/ml and not more than 250 U/ml, a physiological buffer and optionally sodium hyaluronate. A related surgical method includes applying the solution directly during surgery to exposed tissue. The solution can also be injected into the synovial cavity of patients with active arthritis as therapeutic orthopaedics.
    Type: Grant
    Filed: January 2, 1991
    Date of Patent: October 12, 1993
    Assignee: Kiyoshi Kita
    Inventors: Kiyoshi Kita, Fumiaki Yoshitomi
  • Patent number: 5221614
    Abstract: A method for determination of biological activity of AT III which comprises mixing a specimen, AT III free-extrinsic coagulation factor-containing plasma, heparin and a prothrombin time-measuring reagent or a factor X-activating reagent and then measuring a coagulation time, and a reagent and plasma to be used therefor.
    Type: Grant
    Filed: October 25, 1991
    Date of Patent: June 22, 1993
    Assignee: Nippon Shoji Kabushiki Kaisha
    Inventor: Masayasu Enomoto
  • Patent number: 5151266
    Abstract: Methods are disclosed for increasing the solubility of antibodies and their radioisotope, toxin, or drug immunoconjugates and for reducing the non-specific uptake of antibody, either conjugated or unconjugated, into the RES organs such as via Fc receptor-mediated mechanisms. The methods involve incubation of the reactive component with amphipathic molecules, such as an anionic detergent, to achieve the desired result. A preferred anionic detergent in this regard is sodium dodecylsulfate.
    Type: Grant
    Filed: December 22, 1988
    Date of Patent: September 29, 1992
    Assignee: NeoRx Corporation
    Inventors: A. Charles Morgan, Jr., Gowsala Pavanasasivam
  • Patent number: 5138034
    Abstract: A method of fractionating plasma protein which comprises treating a plasma protein-containing material in the following sequence of steps, provided that steps (ii) through (v) may be performed in an optional order: (i) freeze-thaw treatment, (ii) treatment at 5 to 10% ethanol concentration, (iii) treatment with an anion exchanger, (iv) affinity chromatography with immobilized lysine, (v) affinity chromatography with immobilized heparin, (vi) treatment at 18 to 30% ethanol concentration, (vii) treatment at 35 to 45% ethanol concentration.
    Type: Grant
    Filed: June 14, 1990
    Date of Patent: August 11, 1992
    Assignee: The Green Cross Corporation
    Inventors: Yahiro Uemura, Kazuo Takechi, Kenji Tanaka
  • Patent number: 5093237
    Abstract: A method for determination of biological activity of AT III by measuring coagulating time of blood plasma comprises mixing a specimen having AT III free-extrinsic coagulation factor-containing plasma, heparin and a prothrombin time-measuring reagent or a factor X-activating reagent and then measuring the coagulation time, and a reagent and plasma to be used therefor.
    Type: Grant
    Filed: November 2, 1989
    Date of Patent: March 3, 1992
    Assignee: Nippon Shoji Kabushiki Kaisha
    Inventor: Masayasu Enomoto
  • Patent number: 5091177
    Abstract: The present invention is concerned with novel monoclonal antibodies which define a glycolipid antigen associated with human non-small cell lung carcinomas ("NSCLC") and certain other human carcinomas. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods. The invention also comprises a method for determining the presence of a malignant condition in lung tissue and other human tissue. The method involves examining the human tissue for the presence of a glycolipid antigen having the characteristics of a ganglio-N-triosylceramide.
    Type: Grant
    Filed: May 11, 1990
    Date of Patent: February 25, 1992
    Assignee: Oncogen
    Inventors: Ingegerd Hellstrom, Joseph P. Brown, Karl E. Hellstrom, Diane Horn, Peter Linsley
  • Patent number: 5084273
    Abstract: An anticoagulant containing as active ingredients protein C or activated protein C and heparin has a high anticoagulant activity which cannot be obtained with activated protein C or heparin alone. The activity of the anticoagulant is further increased by addition of AT III.
    Type: Grant
    Filed: December 21, 1990
    Date of Patent: January 28, 1992
    Assignee: Hoechst Japan Limited
    Inventor: Keizo Hirahara
  • Patent number: 5053492
    Abstract: Monoclonal antibodies to Mojave toxin and use for isolation of cross-reacting proteins in Crotalus venoms are disclosed. Hybridomas secreting monoclonal antibodies against Mojave toxin were established. The antibodies were used for identifying cross-reacting proteins in individual C. s. scutulatus and other Crotalus venoms and to isolate Mojave toxin. The antibodies recognized five bands with a pI range from 5.1 to 6.1 in immunoblots of electrofocused crude venom and Mojave toxin purified by immunoaffinity chromatography. The specificity of the antibodies was for the basic subunit of the toxin which resolved into four bands of pI between 9.3 and 9.6. Individual C. s. scutulatus venoms of snakes from Texas and southern Arizona had multiple bands with pI's ranging from 4.9 to 6.3. Cross-reacting proteins were also recognized by antibodies in the electrophoresed venoms of C. basiliscus, C. d. durissus, C. d. terrificus, C. h. horridus, and C. v.
    Type: Grant
    Filed: August 7, 1986
    Date of Patent: October 1, 1991
    Assignee: Board of Regents, The University of Texas System
    Inventors: Eppie D. Rael, Richard J. Salo
  • Patent number: 4945054
    Abstract: The present invention relates to a process for separating and purifying proteases and antiproteases. This process is characterized in that there are placed in contact an insoluble cross-linked polymer including in its chain the group --SO.sub.3 R.sub.1 -- and/or the group --SO.sub.2 R.sub.2 -- in which R.sub.1 denotes a hydrogen atom or metal and R.sub.2 denotes the remainder of an amino acid linked to the --SO.sub.2 -- bridge through its amine --NH--, function, with the solution containing proteases and antiproteases or their complex; separating the polymer which has absorbed the desired protein, washing it carefully with the buffer, desorbing the absorbed protein by a solution of a polycationic compound in the case of T or by an albumin solution in the case of AT or of the complex T-AT, and isolating the protein, if desired, by known means, such as, especially, freeze drying. The invention is useful for studying the mechanism of blood coagulation.
    Type: Grant
    Filed: May 17, 1983
    Date of Patent: July 31, 1990
    Assignee: Commissariat a l'Energie Atomique
    Inventors: Christine Fougnot, Marcel Jozefowicz, Robert D. Rosenberg
  • Patent number: 4900720
    Abstract: To maintain an almost unchanged plasma-protein profile in a patient subsequent to plasma exchange, the plasma-exchange medium contains the most essential human serum proteins, except for the coagulation factors, at a concentration of 75 g/l.
    Type: Grant
    Filed: April 6, 1987
    Date of Patent: February 13, 1990
    Assignee: Boitest Pharma GmbH
    Inventor: Ronald Kotitschke
  • Patent number: 4883784
    Abstract: The administration of Factor I and/or Factor H to a mammal has been found to alleviate or prevent such autoimmune diseases as systemic lupus erythematosus, rheumatoid arthritis and glomerulonephritis.
    Type: Grant
    Filed: April 13, 1988
    Date of Patent: November 28, 1989
    Assignee: Sankyo Company Limited
    Inventor: Isao Kaneko
  • Patent number: 4749783
    Abstract: Preparation of active therapeutic proteins comprising two essential steps. In the first step an active protein source is treated under conditions sufficient to inactivate any viruses present (e.g. via heat or chemical treatment). In the second step, the treated active protein source of moderate purity is then treated under conditions sufficient to remove impurities as well as denatured (once active) proteins resulting from the viral inactivation step. In an illustrative embodiment, a biologically active protein such as antithrombin is treated under conditions sufficient to assure viral inactivation and minimal antithrombin deactivation. After the viral inactivation, the antithrombin is contacted with immobilized heparin to complex only the active antithrombin which is then eluted by known means and processed further (e.g., to include desired excipients and then freeze dried).
    Type: Grant
    Filed: July 11, 1986
    Date of Patent: June 7, 1988
    Assignee: Miles Laboratories, Inc.
    Inventors: Robert E. Jordan, Jaleh Kilpatrick
  • Patent number: 4727027
    Abstract: Biological compositions are decontaminated by treatment with furocoumarin derivatives and irradiation under particular conditions in which the proteins retain their original physiological activities and any pathogenic microorganisms and polynucleotide fragments thereof are rendered inactive. It has been found that reduction of the amount of dissolved oxygen in the treatment solution substantially inhibits denaturation of the proteins.
    Type: Grant
    Filed: October 7, 1985
    Date of Patent: February 23, 1988
    Assignee: Diamond Scientific Co.
    Inventors: Gary P. Wiesehahn, Richard P. Creagan