Urokinase Patents (Class 435/215)
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Patent number: 4997766Abstract: Hybrid, third generation, plasminogen activators containing plural, heterologous polypeptide kringles prepared by recombinant DNA techniques as well as the genes coding for the activators. Vectors containing those genes and a method for using the plasminogen activators as thrombolytic agents, are disclosed.Type: GrantFiled: November 14, 1989Date of Patent: March 5, 1991Assignee: American Home Products CorporationInventors: Paul P. Hung, Narender K. Kalyan, Shaw-guang L. Lee
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Patent number: 4992274Abstract: A fibrinolytically active hybrid protein which comprises one chain of a 2-chain protease linked to a chain of a different 2-chain protease, or to the same chain of the same protease, at least one of the chains in the hybrid protein being derived from a fibrinolytically active protease, such that the hybrid protein has a catalytic site essential for fibrinolytic activity which is optionally blocked by a removable blocking group.Type: GrantFiled: February 22, 1988Date of Patent: February 12, 1991Assignee: Beecham Group p.l.c.Inventors: Jeffery H. Robinson, Ian Dodd
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Patent number: 4946785Abstract: The thermal degradation of urokinase in an aqueous solution is suppressed by heating an aqueous solution containing urokinase in the presence of citric acid or a water-soluble salt thereof such as sodium, potassium or lithium citrate at about 60.degree. C. for about 10 hours.Type: GrantFiled: June 17, 1988Date of Patent: August 7, 1990Assignee: Japan Chemical Research Co., Ltd.Inventors: Hajime Hiratani, Satoshi Nishimuro, Koichiro Nakanishi, Masaichi Ota, Hiroshi Matsumoto
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Patent number: 4920051Abstract: Disclosed is a method of recovering urokinase compounds from media and cell extracts. The method comprises contacting the urokinase compound-containing solution with a silicaceous matrix material comprising covalently bound polymer having plural anionic groups. Selective elution of the urokinase compound can produce elutants of high specific activity. The method can succeed in recovering greater than 90% of the urokinase activity from the crude solution.Type: GrantFiled: June 10, 1988Date of Patent: April 24, 1990Assignee: Damon Biotech, Inc.Inventors: Timothy Edmunds, Susan F. Foley
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Patent number: 4916071Abstract: Hybrid, third generation, plasminogen activators containing plural, heterologous polypeptide kringles prepared by recombinant DNA techniques as well as the genes coding for the activators, Vectors containing those genes and a method for using the plasminogen activators as thrombolytic agents, are disclosed.Type: GrantFiled: July 11, 1986Date of Patent: April 10, 1990Assignee: American Home Products CorporationInventors: Paul P. Hung, Narender K. Kalyan, Shaw-guang L. Lee
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Patent number: 4892826Abstract: A process for making urokinase derivatives having a sulfhydryl group incorporated into a remnant of urinary plasminogen activator. The process comprises reducing disulfide bridges in the presence of arginine and incorporating a desired compound having a sulfhydryl containing group into the structure through the formation of a disulfide bridge.Type: GrantFiled: October 11, 1988Date of Patent: January 9, 1990Assignee: Abbott LaboratoriesInventors: Gene A. Homandberg, Thanda Wai
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Patent number: 4889808Abstract: Disclosed herein is a method of enhancing the production of tissue plasminogen activator (t-PA) and single chain urokinase plasminogen activator (SCU-PA) by normal human lung diploid fibroblast cells in a serum-free medium. The method comprises the addition of heparin (or low molecular weight heparin) and an endothelial cell growth factor to the culture medium.Type: GrantFiled: September 17, 1986Date of Patent: December 26, 1989Assignee: American Home ProductsInventor: Ruth Rappaport
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Patent number: 4880776Abstract: A hybrid protein which comprises plasmin A-chain linked to urokinase B-chain, the catalytic site of which is blocked by a removable blocking group.Type: GrantFiled: March 25, 1988Date of Patent: November 14, 1989Assignee: Beecham Group p.l.c.Inventors: Jeffery H. Robinson, Ian Dodd
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Patent number: 4851345Abstract: This invention discloses a fibrinophilic urokinase complex which is a complex of urokinase with a urokinase inhibitor or tissue activator inhibitor and has a molecular weight of 97,500.+-.3,000 and a method for the production of this fibrinophilic urokinase complex from urine. The urokinase complex can be used, as a thrombolytic agent exhibiting an outstanding ability to dissolve thrombus.Type: GrantFiled: September 11, 1986Date of Patent: July 25, 1989Assignee: Terumo Kabushiki KaishaInventors: Shigeru Hayashi, Kaneo Yamada
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Patent number: 4841023Abstract: There is disclosed a process for rendering a labile protein-containing composition, substantially free of lipid-containing viruses without incurring substantial protein denaturation comprising contacting said composition with an effective amount of a fatty acid or a soluble ester, alcohol or a salt thereof for a sufficient period of time to inactivate virus contained therein.Type: GrantFiled: June 25, 1986Date of Patent: June 20, 1989Assignee: New York Blood Center, Inc.Inventor: Bernard Horowitz
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Patent number: 4837022Abstract: A composition containing a tissue Plasminogen Activator (tPA) which comprises a partial hydrolyzate of gelatin cross-linked to a diisocyanate as an essential ingredient; or alternatively a partial hydrolyzate of gelatin cross-linked to a diisocyanate and one or more of a basic amino acid or salt thereof. The composition enhances the solubility of the tPA in water, thereby making the tPA further available in the treatment of circulatory diseases caused by thrombi.Type: GrantFiled: September 10, 1986Date of Patent: June 6, 1989Assignee: Eisai Co., Ltd.Inventors: Fumio Kakimoto, Naoki Asakawa, Yasuo Ishibashi, Yasuo Miyake
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Patent number: 4766075Abstract: Human tissue phasminogen activator (t-PA) is produced in useful quantities using recombinant DNA techniques. The invention disclosed thus enables the production of t-PA free of contaminants with which it is ordinarily associated in its native cellular environment. Methods, expression vehicles and various host cells useful in its production are also disclosed.Type: GrantFiled: April 7, 1983Date of Patent: August 23, 1988Assignee: Genentech, Inc.Inventors: David V. Goeddel, William J. Kohr, Diane Pennica, Gordon A. Vehar
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Patent number: 4753879Abstract: Modified human tissue plasminogen activators, the DNA sequences coding on expression for them and methods of making them in hosts transformed with those DNA sequences. The single chain form of these modified human t-PAs, t-PA (Lys 277.fwdarw.X), has a longer half life than the single chain form of native, or recombinant, t-PA, yet, in the two chain form these modified t-PAs have substantially the same affinity for fibrin and substantially the same activity as the two chain form of native, or recombinant, t-PA.Type: GrantFiled: August 27, 1984Date of Patent: June 28, 1988Assignee: Biogen N.V.Inventors: Joseph J. Rosa, Margaret D. Rosa
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Patent number: 4741903Abstract: A derivative of a fibrinolytic enzyme in which the catalytic site on the enzyme which is responsible for fibrinolytic activity is blocked by a human protein attached thereto by way of a reversible linking group.Type: GrantFiled: April 15, 1987Date of Patent: May 3, 1988Assignee: Beecham Group p.l.c.Inventor: Richard A. G. Smith
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Patent number: 4708944Abstract: A protease adsorbent wherein valyl-glycyl-argininal is bound to a water-insoluble carrier and a process for purifying TPA utilizing the same.Type: GrantFiled: June 28, 1985Date of Patent: November 24, 1987Assignee: Nippon Kayaku Kabushiki KaishaInventors: Tetsuya Someno, Kazuo Kato, Yasushi Takahashi, Shinichi Ishii, Tomio Takeuchi, Hamao Umezawa
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Patent number: 4673573Abstract: A fibrinolytically active protein conjugate comprising at least one optionally blocked fibrinolytic enzyme linked by way of a site other than the catalytic site responsible for fibrinolytic activity to at least one human protein.Processes from making the conjugates and pharmaceutical compositions containing them are also described.Type: GrantFiled: January 9, 1985Date of Patent: June 16, 1987Assignee: Beecham Group p.l.c.Inventors: Harry Ferres, Richard A. G. Smith, Andrew J. Garman
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Patent number: 4661453Abstract: A process for the production of a tissue plasminogen activator obtained from cultured rat prostate adenocarcinoma cells. The techniques described lead to enhanced production of the tissue plasminogen activator for markedly prolonged periods of time. The tissue plasminogen activator so produced may be used for the treatment of thrombosis.Type: GrantFiled: June 19, 1984Date of Patent: April 28, 1987Assignee: American Biogenetic Sciences, Inc.Inventor: Morris Pollard
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Patent number: 4640835Abstract: Derivatives of a nonimmunogenic plasminogen activator which comprises at least one polyalkylene glycol group chemically bonded with at least one coupling agent to amino acid side chains of said plasminogen activator, wherein said polyalkylene glycol has a molecular weight of about 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.The plasminogen activator derivatives have an extended circulating life in the mammalian bloodstream and also inhibit the formation of thrombus in the same.Type: GrantFiled: October 28, 1983Date of Patent: February 3, 1987Assignee: Nippon Chemiphar Company, Ltd.Inventors: Kimihiro Shimizu, Tsuguji Nakahara, Taketoshi Kinoshita, Jun Takatsuka, Michiko Igarashi
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Patent number: 4629694Abstract: This invention relates to a method for determining fibrinolytic activation in human blood and to a method to distinguish between tissue (e.g. vascular) plasminogen activator and urokinase-like plasminogen activator contributions to fibrinolytic activation.Broadly, the method of the invention relates to detecting the level of plasmin-plasmin inhibitor complexes in blood plasma samples before and after clotting thereof; a greater increase in the complex level in the clotted sample as compared to non-clotted samples indicating the presence of circulating tissue plasminogen activator, with substantially identical levels of increase of complex in both the clotted and unclotted samples indicating the sole presence of urokinase-type plasminogen activator in the sample.Type: GrantFiled: July 12, 1983Date of Patent: December 16, 1986Assignee: Cornell Research Foundation, Inc.Inventor: Peter C. Harpel
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Patent number: 4604357Abstract: The invention relates to disinfectant urinal block means useful for collection of pooled urine and method of using the block means to provide in service release, of an antimicrobial agent component from the block means into the pool for effective inhibition of bacterial growth and consequent enzymatic degradation of wanted proteins contained in the pool.Type: GrantFiled: April 13, 1984Date of Patent: August 5, 1986Assignee: Enzymes of AmericaInventors: Denis M. Callewaert, Earl J. Braxton
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Patent number: 4600580Abstract: A derivative of a fibrinolytic enzyme in which the catalytic site on the enzyme which is responsible for fibrinolytic activity is blocked by a human protein attached thereto by way of a reversible linking group.Type: GrantFiled: December 21, 1984Date of Patent: July 15, 1986Assignee: Beecham Group P.L.C.Inventor: Richard A. G. Smith
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Patent number: 4568544Abstract: An aqueous solution of a tissue plasminogen activator dissolved therein at an increased concentration which comprises an aqueous medium and, dissolved therein, a high purity tissue plasminogen activator and at least one dissolution aid selected from the group consisting of lysine, ornithine and salts thereof, and a method for increasing a solubility of a high purity tissue plasminogen activator in an aqueous medium comprising adding said at least one dissolution aid to an aqueous solution of a high purity tissue plasminogen activator. The present aqueous solution contains a high purity tissue plasminogen activator dissolved therein at an increased concentration and the activity of the tissue plasminogen activator can be maintained during handling and storage of the aqueous solution.Type: GrantFiled: February 26, 1985Date of Patent: February 4, 1986Assignee: Asahi Kasei Kogyo Kabushiki KaishaInventors: Akio Hasegawa, Shuhei Kondo
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Patent number: 4564596Abstract: Urokinase derivatives comprise urokinase covalently bonded with fibrinogen or urokinase covalently bonded with fibrinogen through an aliphatic diamine and correspond to the general formula: ##STR1## wherein P is fibrinogen, E is urokinase, R is absent or stands for ##STR2## wherein n is 1-12, with a molecular mass of from 360,000 to 440,000 D, a content of protein of 10 to 30% by mass, an esterase catalytic activity of 30-60%.These derivatives have an increased affinity to fibrin and feature a prolonged fibrinolytic effect.Type: GrantFiled: January 3, 1985Date of Patent: January 14, 1986Inventors: Alexandr V. Maximenko, Elena G. Tischenko, Vladimir P. Torchilin, Vladimir N. Smirnov, Evgeny I. Chazov
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Patent number: 4564472Abstract: A radioactive diagnostic agent which comprises a physiologically active substance and a radioactive metallic element combined with a compound of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are each hydrogen, C.sub.1 -C.sub.3 alkyl or phenyl. The agent is characteristic in having a high stability even after being administered into a human body and showing the substantially the same behavior as the physiologically active substance itself in a human body.Type: GrantFiled: June 30, 1983Date of Patent: January 14, 1986Assignee: Nihon Medi-Physics Co., Ltd.Inventors: Nobuo Ueda, Susumu Kondo, Masaaki Hazue
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Patent number: 4557863Abstract: The invention relates to a device useful when installed in a urinal for collection of urinary proteins. The adsorbent means includes a conduit for gravity feed passage of urine streams. The conduit has permeable layers in series containing a slow releasing antimicrobial agent and an adsorbent for urinary proteins such that for collection puropses wanted proteins are adsorbed without odor or loss due to bacterial degradation.Type: GrantFiled: April 13, 1984Date of Patent: December 10, 1985Inventors: Denis M. Callewaert, Earl J. Braxton
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Patent number: 4552760Abstract: A method for stabilizing a tissue plasminogen activator which involves adding to an aqueous solution or powder containing a tissue plasminogen activator an effective amount of a purified gelatin is disclosed. A stable aqueous solution or powder which contains a tissue plasminogen activator and an effective amount of a purified gelatin is also disclosed. The method and composition eliminate the problem of adsorption of tissue plasminogen activator to various laboratory equipment, and also prevent the conversion of the single-chain tissue plasminogen activator into a double-chain tissue plasminogen activator.Type: GrantFiled: April 23, 1984Date of Patent: November 12, 1985Assignees: Asahi Kasei Kogyo Kabushiki Kaisha, Kowa Co., Ltd.Inventors: Akira Murakami, Hideo Yoshizaki
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Patent number: 4545988Abstract: This invention provides a urokinase complex adsorbable by fibrin characterized in that it comprises heavy chain of high molecular weight urokinase as coupled with heavy chain of plasmin by one or more S-S bonds and a process for preparing the same.Type: GrantFiled: December 18, 1984Date of Patent: October 8, 1985Assignee: Otsuka Pharmaceutical Co., Ltd.Inventors: Yasuo Nakayama, Wasei Miyazaki, Masanao Shinohara
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Patent number: 4537852Abstract: The present invention relates to a process for the production of human urokinase. More precisely, the present invention relates to a process for the mass production of human urokinase, comprising in vivo multiplication of human cells capable of producing human urokinase, using the nutrient body fluid of a non-human warm-blooded animal, and exposure of the multiplied human cells to an urokinase inducer. The human urokinase present production according to the invention is much higher than that attained by conventional methods; thus, human urokinase can be used in sufficient amount in the prevention and treatment of human diseases.Type: GrantFiled: November 12, 1981Date of Patent: August 27, 1985Assignee: Kabushiki Kaisha Hayashibara Seibutsu Kagaku KenkyujoInventor: Kaname Sugimoto
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Patent number: 4536391Abstract: This invention provides a process for preparing a fibrin-adsorable protein-urokinase complex characterized by reacting a protein adsorbable by fibrin with urokinase in the presence of a protein coupling reagent represented by the formula ##STR1## wherein R is phenylene or cycloalkylene, A is lower alkylene, B is lower alkylene which may optionally be substituted by lower alkylthio or phenyl-lower alkylthio, and l, m and n are each 0 or 1 provided that l, m and n are not 0 at the same time.The complex is useful as a thrombolytic agent.Type: GrantFiled: November 15, 1983Date of Patent: August 20, 1985Assignee: Otsuka Pharmaceutical Co.Inventors: Wasei Miyazaki, Tsuneo Sato, Yasuo Nakayama, Tadao Sato
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Patent number: 4525465Abstract: A biospecific adsorbent comprising pyroglutamyl-lysyl-leucyl-argininal combined with a water-insoluble support is provided. This biospecific adsorbent is useful as an adsorbent for use in affinity chromatography and can be utilized for the purification of proteases such as urokinase.Type: GrantFiled: October 7, 1983Date of Patent: June 25, 1985Assignee: Nippon Kayaku Kabushiki KaishaInventors: Tetsuya Someno, Kazuo Kato, Tetsushi Saino, Shinichi Ishii, Tomio Takeuchi, Hamao Umezawa
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Patent number: 4495285Abstract: A derivative of a human-originated non-immunogenic plasminogen activator is disclosed which comprises at least one polyalkylene glycol attached with at least one coupling agent to amino acid side chains of said plasminogen activator, said polyalkylene glycol having a molecular weight of 200-20,000 and optionally containing one or more alkyl and/or alkanoyl groups as substituents. Also disclosed are a process for producing such derivative and a thrombolytic agent containing such derivative.Type: GrantFiled: October 27, 1982Date of Patent: January 22, 1985Inventors: Kimihiro Shimizu, Tsuguji Nakahara, Taketoshi Kinoshita
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Patent number: 4381346Abstract: The existence of high fibrin-affinity urokinase is discovered by an isolation procedure using fibrin precipitated on an adsorptive-solid matrix. By the method described, the high affinity form of plasminogen activator can be isolated directly from urine or from kidney tissue culture medium. The method is economical and provides a relatively high yield of the activator. The high affinity that this plasminogen activator has for fibrin is a property that makes it an improved thrombolytic agent and when radiolabelled provides a new diagnostic agent for the specific detection of fibrin thrombi through nuclear scanning. The newly-isolated plasminogen activator has the following characteristics: a molecular weight of about 56,000 Daltons, a specific activity of about 40,000-50,000 CTA units/mg, the appearance of a single chain structure and a high affinity for fibrin.Type: GrantFiled: September 2, 1980Date of Patent: April 26, 1983Inventors: Syed S. Huasin, Boguslaw Lipinski, Victor Gurewich
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Patent number: 4378435Abstract: A process for providing enzyme activity to the surface of an article is described, comprising forming a film on the surface of the article, said film comprising an acid anhydride group-containing polymer and a polyol, wherein the acid anhydride groups are partially reacted with the polyol, and thereafter reacting the unreacted acid anhydride groups with an enzyme. Such an article provided with enzyme activity on the surface can be used for the production of food, medicines, etc., and as a medical material.Type: GrantFiled: October 27, 1980Date of Patent: March 29, 1983Assignee: Unitika, Ltd.Inventors: Kunihiko Takagi, Yasunori Yabushita
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Patent number: 4370417Abstract: The present invention provides a deoxyribonucleic acid (DNA) segment related to a human plasminogen activator gene. The segment is inserted into a plasmid vector which in turn can be incorporated into a bacterium or other microorganism. The bacterium can then be cultured to produce a plasminogen activator protein having properties of human urokinase.Type: GrantFiled: April 3, 1980Date of Patent: January 25, 1983Assignee: Abbott LaboratoriesInventors: Paul P. Hung, Shaw-Guang Lee, Ranajit Roychoudhury, Barry J. Ratzkin, W. Jurgen Schrenk, Michael C. Chen
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Patent number: 4349630Abstract: A heat-resistant water soluble derivative of urokinase is prepared which comprises urokinase covalently bonded to a copolymer of acrylamide and acrylic acid having a molecular weight of 10,000 to 200,000 and a content of acrylic acid of 1% to 2%. The derivative contains 15% to 35% urokinase and has an esterase and amidolytic activity of from 10% to 80%.Type: GrantFiled: August 27, 1980Date of Patent: September 14, 1982Inventors: Alexandr V. Maximenko, Vladimir P. Torchilin, Vladimir N. Smirnov, Evgeny I. Chazov
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Patent number: 4326033Abstract: Described is a structurally modified urokinase which is biologically active over an extended time period in comparison to native urokinase. The extended activity permits the administration of lower doses of urokinase when it is used in the treatment of thromboembolic diseases. Methods of appropriately modifying the structure of urokinase are described.Type: GrantFiled: May 5, 1980Date of Patent: April 20, 1982Assignee: Abbott LaboratoriesInventors: William H. Holleman, Shaw-Guang Lee, Paul P. Hung
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Patent number: 4321363Abstract: Highly pure urokinase can be produced by affinity chromatography on a novel adsorbent which comprises a water insoluble carrier and a ligand united to the carrier. The ligand is shown by the general formula ##STR1## wherein X is oxygen, sulfur or imino group, and R is amino or carboxyl group.Type: GrantFiled: February 21, 1980Date of Patent: March 23, 1982Assignee: Nippon Soda Company LimitedInventors: Daigaku Takiguchi, Eiji Itou, Hiroaki Nakamura, Izumi Kumita
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Patent number: 4317882Abstract: A plasminogen activator having a molecular weight of 45,000 to 68,000 is formed as a single fraction in the cells of human kidney or lung, and is separated and recovered with good efficiency without reducing its molecular weight. The pH of a solution to be contacted with said cells and the concentration of dissolved oxygen should be maintained within suitable ranges in order to form the plasminogen activator having a molecular weight of 45,000 to 68,000 as a single fraction. Furthermore, by properly adjusting the residence time of the solution with the cells, the activator can be formed over a long period of more than 40 days. To separate the activator, the pH of the solution in the separating step is maintained preferably at 4 to 12. By causing a metal chelating agent to be present in the solution in the separating step, the plasminogen activator can be obtained without reducing its molecular weight.Type: GrantFiled: April 25, 1980Date of Patent: March 2, 1982Assignee: Asahi Kasei Kogyo Kabushiki KaishaInventors: Sadayuki Horiguchi, Akio Hasegawa, Mitsuru Shibukawa
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Patent number: 4315002Abstract: A process for the preparation of a solid pharmaceutical or diagnostic composition in which the active substance and dextran are dissolved in water, the solution is placed in a mold and is thereafter lyophilized to form a solid abrasion-resistant tablet which can further be compressed to reduce its rate of disintegration in water. The invention is also directed to the pharmaceutical or diagnostic agent produced by this process.Type: GrantFiled: May 30, 1980Date of Patent: February 9, 1982Assignee: BASF AktiengesellschaftInventor: Robert Maurer
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Patent number: 4286063Abstract: A method for producing a thrombolytic preparation characterized in that among treatment conditions in the urokinase production pH is maintained within the neutral or weakly alkaline range throughout each treatment step to produce a thrombolytic preparation containing urokinase having a molecular weight of 54,000.+-.10,000 as major ingredient.Type: GrantFiled: December 19, 1979Date of Patent: August 25, 1981Assignee: The Green Cross CorporationInventor: Tadakazu Suyama
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Patent number: 4273873Abstract: Antithrombogenic polymeric materials are prepared by bonding a synthetic fibrinolytic compound or a combination of a synthetic fibrinolytic compound and a fibrinolytic enzyme to a polymeric material. Bonding is preferably by covalent or ionic bonding. The antithrombogenic polymeric materials are useful for preparing various types of medical articles that come into contact with blood.Type: GrantFiled: October 25, 1977Date of Patent: June 16, 1981Assignee: Unitika Ltd.Inventors: Akio Sugitachi, Kunihiko Takagi, Yasunori Yabushita
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Patent number: 4259447Abstract: There is provided a process for the production of pure, concentrated urokinase starting from a crude urokinase solution. The crude urokinase solution is contacted in a medium having a pH of .gtoreq.6 with a porous solid matrix having a high specific surface area on whose surface there is immobilized aprotinin. Subsequently the urokinase adsorbed in this manner is eluted in an elution agent having a pH.ltoreq.4.5. There are obtained highly concentrated and very pure solutions of urokinase. The urokinase is used in medicine as a pharmaceutical for the dissolving of fibrinous clots and coagulums.Type: GrantFiled: June 29, 1979Date of Patent: March 31, 1981Assignee: Alpha Patent LimitedInventor: Robert Hafeli
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Patent number: 4259448Abstract: A novel protein adsorbent having a group of the general formula ##STR1## wherein X is hydrogen, halogen, amino, lower alkyl or lower alkoxycarbonyl as a ligand, is useful for the purification of urokinase by hydrophobic chromatography, particularly for the removal of such kind of pyrogen that is scarcely removed by affinity chromatography on the ordinal adsorbent of urokinase.Type: GrantFiled: October 10, 1979Date of Patent: March 31, 1981Assignee: Nippon Soda Company, Ltd.Inventors: Hiroaki Nakamura, Izumi Kumita, Yoshiji Sugita, Hiedo Takagi
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Patent number: 4258030Abstract: Disclosed is a urokinase preparation for oral administration which is effective for remedy of thrombosis such as cerebral thrombosis and cardiac infarction. This preparation comprises urokinase and, incorporated therein, an enzyme inhibitor.Type: GrantFiled: March 7, 1979Date of Patent: March 24, 1981Assignee: Zeria-Shinyaku Kogyo Kabushiki KaishaInventors: Koji Sasaki, Yasukazu Harada
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Patent number: 4244943Abstract: A method for preparing a stable urokinase injection by the liophilization of urokinase which comprises liophilizing an aqueous solution containing urokinase, human serum albumin and one or more amino acid compounds selected from polar amino acids and salt thereof. The urokinase injection obtained according to this method is excellent in the storing stability as compared with conventional urokinase preparations for injection.Type: GrantFiled: May 9, 1979Date of Patent: January 13, 1981Assignee: Sumitomo Chemical Company, LimitedInventors: Yoshiya Yamahira, Keiji Fujioka, Yoshiko Okuzawa, Seiko Miura, Shigeji Sato
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Patent number: 4232124Abstract: Production of plasminogen activator from human diploid lung cells through cultivation in an aqueous nutrient medium containing an inducer of activator production.Lactalbumin hydrolysate is an active inducer, and is used in 0.1-1.0% w/v concentration in the medium.Type: GrantFiled: April 23, 1979Date of Patent: November 4, 1980Inventor: George F. Mann
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Patent number: 4225675Abstract: Highly pure urokinase can be produced by affinity chromatography on the adsorbent. The adsorbent comprises water insoluble carrier to which the group of the general formula whereinn is an integer of 5 to 12,m is zero or one, andR is (m- or p-) guanidino or (m- or p-) amidino group; is bound.Type: GrantFiled: January 3, 1978Date of Patent: September 30, 1980Assignee: Nippon Soda Company, Ltd.Inventors: Hiroaki Nakamura, Izumi Kumita, Yoshiji Sugita, Hiedo Takagi
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Patent number: 4190708Abstract: The yield of urokinase produced by cell culture of kidney cells is improved by incorporating in the cell culture medium an elevated level of phenylalanine.Type: GrantFiled: May 24, 1978Date of Patent: February 26, 1980Assignee: Monsanto CompanyInventors: Mau-Jung Kuo, Margaret J. Reents, Joseph Feder
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Patent number: 4189350Abstract: A process for purifying urokinase by contacting a crude urokinase-containing solution with a strongly acidic cation exchanger having sulfonic acid groups and adjusted to the NH.sub.4.sup.+ type to adsorb urokinase on said cation exchanger and then eluting urokinase from said exchanger, characterized in that urea is previously added to the crude urokinase-containing solution in such a rate that the final molar concentration of urea in the solution is 3 to 8 M. This process is capable of providing purified urokinase having substantially constant and high specific activity from a crude urokinase-containing solution with a high recovery regardless of purity of the crude urokinase.Type: GrantFiled: June 1, 1978Date of Patent: February 19, 1980Assignee: Sumitomo Chemical Company, LimitedInventors: Hideki Yanagi, Yasuo Bai, Junichi Yoshikawa, Shigeo Ogino
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Patent number: RE32271Abstract: The existence of high fibrin-affinity urokinase is discovered by an isolation procedure using fibrin precipitated on an adsorptive-solid matrix. By the method described, the high affinity form of plasminogen activator can be isolated directly from urine or from kidney tissue culture medium. The method is economical and provides a relatively high yield of the activator. The high affinity that this plasminogen activator has for fibrin is a property that makes it an improved thrombolytic agent and when radiolabelled provides a new diagnostic agent for the specific detection of fibrin thrombi through nuclear scanning. The newly-isolated plasminogen activator has the following characteristics: a molecular weight of about 56,000 Daltons, a specific activity of about 40,000-50,000 CTA units/mg, the appearance of a single chain structure and a high affinity for fibrin.Type: GrantFiled: April 26, 1985Date of Patent: October 28, 1986Inventors: Syed S. Husain, Boguslaw Lipinski, Victor Gurewich