Thrombin Patents (Class 435/214)
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Patent number: 5648228Abstract: The present invention provides a method for measuring the activity of tested substances utilizing a reconstituted plasma kallikrein-kinin system. A series of enzymatic reactions is started wherein an activation of a blood coagulation factor XII is an initiating reaction. The series of reactions is started in the presence of the tested substance in the reconstituted plasma kallikrein-kinin system. Then, the series of reactions is stopped and the physiologically active substance produced in the reaction series is quantitatively determined. In the activity measuring method of the present invention, the real activity (a promoting or inhibiting ability) of the tested substance against the production of the produced physiologically active substance can be easily, simply, quickly and precisely measured. In the reconstituted plasma kallikrein-kinin reaction system the contaminating other factors are substantially removed.Type: GrantFiled: August 4, 1994Date of Patent: July 15, 1997Assignee: Nippon Zoki Pharmaceutical Co., Ltd.Inventors: Katsumi Nishikawa, Hitoshi Kawakubo
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Patent number: 5643192Abstract: A fibrin glue includes a fibrinogen component and a thrombin component, both prepared from single donor plasma. The plasma is precipitated to produce a precipitate containing fibrinogen and a supernatant containing the thrombin. The precipitate may be resuspended in a small volume of supernatant and used as the fibrinogen component. The supernatant is further treated by clotting to convert residual fibrinogen to fibrin and filtration to remove the fibrin. The resulting serum can be used as the thrombin component.Type: GrantFiled: April 6, 1995Date of Patent: July 1, 1997Assignee: Hamilton Civic Hospitals Research Development, Inc.Inventors: Jack Hirsh, Marilyn Johnston, Kevin Teoh
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Patent number: 5595735Abstract: A hemostatic paste composition comprising a hemostatic effective amount of thrombin in a polyethylene glycol base which is preferably prepared by admixing an aqueous solution of thrombin and polyethylene glycol and freeze-drying the mixture to remove substantially all of the water to yield a viscous water soluble paste of fine particles of thrombin uniformly dispersed throughout the polyethylene glycol base, and methods of its use to provide hemostasis to a hemorrhaging site of a mammal.Type: GrantFiled: May 23, 1990Date of Patent: January 21, 1997Assignee: Johnson & Johnson Medical, Inc.Inventors: Lowell Saferstein, Stephen J. Wolf
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Patent number: 5585350Abstract: A novel thrombin inhibitory protein from ticks with a molecular weight of about 26000 dalton and the partial amino acid sequences Val-Ala-Lys-Phe-Ala-X-Asn-Ser-Gly-Ser-Glu-Thr-Gly (SEQ ID NO: 8), His-Ala-Y-Phe-Glu (SEQ ID NO: 3), Arg-Val-Ser-Asp-Phe-Glu (SEQ ID NO: 4), Phe-Val-Tyr-Thr-Ile-Glu (SEQ ID NO: 6), where X and Y can be identical or different and each is a naturally occurring amino acid, is suitable for controlling diseases.Type: GrantFiled: March 18, 1994Date of Patent: December 17, 1996Assignee: BASF AktiengesellschaftInventors: Thomas Friedrich, Wolfgang Koerwer, Burkhard Kroeger, Siegfried Bialojan
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Patent number: 5571708Abstract: A new chimeric plasminogen activator with high fibrin affinity was designed to bind to a fibrin clot and initiate clot destruction in the presence of thrombin, but not plasmin. The chimeric molecule has an antibody variable region having a fibrin-specific antigen binding site and a single chain urokinase region having a thrombin activation site but not a plasmin activation site. The preferred embodiment, 59D8-ScuPA-T, has an N-terminal fragment of an anti-fibrin antibody (59DB) and a C-terminal thrombin-activatable low molecular weight single-chain urokinase plasminogen activator (scuPA-T). The scuPA-T portion was obtained by deletion of two amino acids (Phe157 and Lys 158) that make up the plasmin activation site from low molecular weight single chain urokinase-type plasminogen activator (scuPA).Type: GrantFiled: April 19, 1993Date of Patent: November 5, 1996Assignee: Bristol-Myers Squibb CompanyInventors: Wen-Pin Yang, Gary R. Matsueda, Shyh-Yu Shaw
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Patent number: 5527692Abstract: Methods are disclosed for producing thrombin. The protein is produced from host cells transformed or transfected with DNA construct(s) containing information necessary to direct the expression of thrombin precursors. The DNA constructs generally include the following operably linked elements: a transcriptional promoter, DNA sequence encoding a gla-domainless prothrombin, and a transcriptional terminator. Thrombin precursors produced from transformed or transfected host cells are activated either in vivo or in vitro.Type: GrantFiled: June 5, 1995Date of Patent: June 18, 1996Assignee: Zymogenetics, Inc.Inventors: Richard D. Holly, Donald C. Foster
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Patent number: 5525498Abstract: An ultra-pure, clear thrombin solution having a high specific activity is described as well as a method of manufacture.Type: GrantFiled: February 22, 1991Date of Patent: June 11, 1996Assignee: Warner-Lambert CompanyInventors: Amal Boctor, Surendra Mehta, Galen Radebaugh
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Patent number: 5514572Abstract: A method for preparing protease-polyethylene glycol adducts is presented wherein the immobilized reversible inhibitor, benzamidine, prevents reaction of activated polyethylene glycol with the active site of the protease. Improved activity against macromolecular substrates is obtained compared to when the benzamidine is in solution during the conjugation reaction.Type: GrantFiled: September 19, 1994Date of Patent: May 7, 1996Assignee: Consiglio Nazionale delle RicercheInventors: Francesco Veronese, Paolo Caliceti, Oddone Schiavon, Sartore Luciana
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Patent number: 5512459Abstract: The method of the invention provides for the formation of a recombinant polypeptide which has been modified at the C-terminal end through the use of a transpeptidation process. The method is suitable for modifying recombinant polypeptides of any source including those which may be commercially available, those derived from recombinant single copy or multicopy polypeptide constructs, or those derived from single or multicopy recombinant fusion protein constructs. The transpeptidation reaction involves contacting an endopeptidase enzyme with a recombinant polypeptide to substitute an addition unit, of one or more amino acids, for a leaving unit, linked to a core polypeptide through a cleavage site recognized by the endopeptidase enzyme. Recombinant polypeptides derived from multicopy polypeptide constructs may be cleaved from the multicopy polypeptide at the N-terminal and C-terminal ends and simultaneously under go substitution of the leaving unit by the desired addition unit.Type: GrantFiled: July 20, 1993Date of Patent: April 30, 1996Assignee: BioNebraska, Inc.Inventors: Fred W. Wagner, Jay Stout, Dennis Henriksen, Bruce Partridge, Shane Manning
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Patent number: 5506127Abstract: A process for the large-scale production of therapeutic grade thrombin of excellent viral safety and storage-stability is carried out by purification of viricide treated crude thrombin by ion-exchange chromatography on a single column using a sulfalkyl-activated polysaccharide, particularly a non-compressible composite medium of sulfoalkyl-activated dextran and silica particles, as the ion exchange medium and using increasing concentrations of phosphate buffer for elution. After recovery of thrombin in the final eluate, the phosphate buffer is exchanged for a stabilizing formulation buffer, and the stabilized thrombin is subjected to viral filtration and optional dry heat treatment for further viral inactivation. The final product has high specific activity and is obtained in good yield.Type: GrantFiled: September 21, 1994Date of Patent: April 9, 1996Inventors: Zbigniew Proba, Teresa Brodniewicz
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Patent number: 5502034Abstract: Methods are disclosed for producing thrombin. The protein is produced from host cells transformed or transfected with DNA construct(s) containing information necessary to direct the expression of thrombin precursors. The DNA constructs generally include the following operably linked elements: a transcriptional promoter, DNA sequence encoding a gla-domainless prothrombin, and a transcriptional terminator. Thrombin precursors produced from transformed or transfected host cells are activated either in vivo or in vitro.Type: GrantFiled: June 5, 1995Date of Patent: March 26, 1996Assignee: Zymogenetics, Inc.Inventors: Richard D. Holly, Donald C. Foster
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Patent number: 5480864Abstract: A modified maxadilan protein exhibits higher biological activity than native maxadilan from the sand fly Lutzomyia longipalpis. A modified maxadilan fusion protein contains a thrombin cleavage site. This enables the production of the modified maxadilan as a fusion protein and recovery of the modified maxadilan after digestion with thrombin. The modified maxadilan is a potent vasodilator.Type: GrantFiled: August 6, 1993Date of Patent: January 2, 1996Assignees: Shiseido Co., Ltd., The General HospitalInventors: Masahiro Tajima, Manami Ohnuma, Ethan L. Lerner
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Patent number: 5476777Abstract: Methods are disclosed for producing thrombin. The protein is produced from host cells transformed or transfected with DNA construct(s) containing information necessary to direct the expression of thrombin precursors. The DNA constructs generally include the following operably linked elements: a transcriptional promoter, DNA sequence encoding a gla-domainless prothrombin, and a transcriptional terminator. Thrombin precursors produced from transformed or transfected host cells are activated either in vivo or in vitro.Type: GrantFiled: December 30, 1992Date of Patent: December 19, 1995Assignee: Zymogenetics, Inc.Inventors: Richard D. Holly, Donald C. Foster
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Patent number: 5474770Abstract: The present invention relates to a biological support for cell cultures formed by the coagulated mixture of a concentrate of plasma proteins and thrombin.The protein concentrate is obtained by precipitating fresh plasma with ethanol and contains balanced proportions of fibrinogen, Factor XIII and fibronectin. The thrombin concentration is adjusted to obtain the desired consistency of the support coagulated in the form of a film.The biological support is preferably used for preparing a culture of keratinocytes, recovering them in the form of a reconstituted tissue and transporting same. The reconstituted tissue is thus particularly suitable for use as a graft.Type: GrantFiled: March 12, 1992Date of Patent: December 12, 1995Assignee: Centre Regional de Transfusion Sanguine de LilleInventors: Herve Broly, Vincent Ronfard
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Patent number: 5453370Abstract: A method for the preparation of a phospholipid-dependent prothrombin activator from the venom of snakes belonging to the Elapidae family, the activator comprising an increased plasma clotting activity in the presence of phospholipids and calcium ions; a reduced activity in the presence of Lupus Anticoagulant; an ability to facilitate clotting in a normal clotting time in the presence of platelet poor plasma, the plasma having normal or decreased levels of factor V, VII, VIII, IX, or X; and a major band with a molecular weight of 40,000 to 60,000 daltons on an SDS gel.Type: GrantFiled: November 30, 1992Date of Patent: September 26, 1995Assignee: Pentapharm AGInventors: Douglas A. Triplett, Kurt Stocker
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Patent number: 5445958Abstract: A method for at least partially separating vitamin K-dependent blood clotting factors from a mixture containing at least one such factor, e.g. a prothrombin complex concentrate, which comprises adsorption of said mixture on to a chelate of a polyvalent metal immobilized on an inert support, e.g. Cu.sup.2 + -primed Chelating Sepharose, followed by elution to yield one or more fractions enriched in respect of one of said factors.Type: GrantFiled: February 23, 1993Date of Patent: August 29, 1995Assignee: National Blood AuthorityInventor: Peter A. Feldman
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Patent number: 5443959Abstract: A dry reagent consisting essentially of (a) a protein having thrombin activity, (b) at least one additive selected from the group consisting of amino acid, a salt thereof and saccharide and optionally (c) magnetic particles, and a method of assaying fibrinogen in an assay sample using the above dry reagent. The dry reagent obviates the time required for preparing a reagent and warming an assay sample, and permits facile fibrinogen assay by only diluting an assay sample. The fibrinogen assay range being broad, the dry reagent substantially obviates the procedure of remeasuring plasma having a fibrinogen concentration outside the assay range of a liquid reagent. The assay result by the dry reagent and that by a liquid reagent well correlate with each other as compared with the result by any known thrombin-containing dry reagent, and the assay by the dry reagent can be performed with good reproducibility in achievement and reliability in measurement.Type: GrantFiled: July 29, 1993Date of Patent: August 22, 1995Assignee: Tokuyama CorporationInventors: Masayoshi Kikuchi, Kenji Kunai, Takafumi Yamada
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Patent number: 5432062Abstract: Prothrombin is cleaved by proteases in the presence of a detergent or certain chaotropic substances to produce thrombin. Under these conditions, controlled and restricted proteolysis occurs such that significant activation without digestion occurs. The chaotropic substances may be urea, guanidinium hydrochloride or a thiocyanate salt. Reversible immobilization of prothrombin on a solid support prior to activation improves the selectivity of the proteolytic activation.Type: GrantFiled: March 30, 1993Date of Patent: July 11, 1995Assignee: Immuno AktiengesellschaftInventor: Peter Turecek
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Patent number: 5427937Abstract: A soluble anticoagulant protein isolated and purified from Ancylostoma hookworms markedly prolongs both the prothrombin time and partial thromboplastin time in clotting assays. The protein has an apparent molecular weight of about 6500 daltons and exhibits amino acid sequence homology to the Kunitz-type serine protease inhibitor family. Chromogenic peptide substrate and clotting time assays indicate that the protein inhibits extrinsic pathway clotting factor VIIa, the enzyme responsible for initiating the human coagulation cascade, and factor Xa in the common pathway of the coagulation cascade.Type: GrantFiled: April 30, 1993Date of Patent: June 27, 1995Inventors: Michael Cappello, Peter J. Hotez, Frank F. Richards, John M. Hawdon
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Patent number: 5401663Abstract: A reagent blood coagulation that causes an increase in turbidity changes when added to a plasma sample containing a substance activating coagulation factor activating such as tissue thromboplastin, phospholipid and thrombin, calcium ion, and molecular substance such as high molecular vinyl and a high molecular polysaccharide. By adding a molecular substance to the reagent, the turbidity change due to blood coagulation is increased, and hence the changing quantity of transmitted light or scattered light increases, thereby making it possible to achieve a more accurate detection. Besides, by adjusting the electric conductivity, pH and osmotic pressure to proper values, the turbidity change due to blood coagulation may be further amplified.Type: GrantFiled: November 18, 1993Date of Patent: March 28, 1995Assignee: Toa Medical Electronics Co., Ltd.Inventor: Masaru Yonemura
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Patent number: 5397704Abstract: An ultra-pure, clear thrombin solution having a high specific activity is described as well as a method of manufacture.Type: GrantFiled: October 12, 1993Date of Patent: March 14, 1995Assignee: Warner-Lambert CompanyInventors: Amal Boctor, Surendra Mehta, Galen Radebaugh
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Patent number: 5354682Abstract: A purified therapeutic grade thrombin is described which is essentially free of lipid envelope viruses, has a specific activity of about 2200 NIH units per milligram of protein to about 3200 NIH units per milligram of protein, is essentially homogeneous and may be produced on a commercial-scale. The thrombin is acceptable from human administration.Type: GrantFiled: February 24, 1993Date of Patent: October 11, 1994Assignee: Baxter International Inc.Inventors: Henry S. Kingdon, Michael J. Griffith, Joyce Lawrence, Roger L. Lundblad
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Patent number: 5352664Abstract: Thrombin is now known to mediate a number of potent biological effects on cells bearing high-affinity thrombin receptors. These effects depend, at least in part, upon receptor occupancy signals generated by thrombin's interaction with the high affinity thrombin receptor. The present inventors have formulated synthetic thrombin derivatives capable of selectively stimulating or inhibiting thrombin receptor occupancy signals. The stimulatory thrombin derivatives to bind to cell surface thrombin receptors and stimulate DNA synthesis in cells treated with non-mitogenic concentrations of alpha-thrombin or phorbol myristate acetate. Thus, these peptides, which have both a thrombin receptor binding domain and a segment of amino acids with a sequence common to a number of serine proteases, appear to generate receptor-occupancy dependent mitogenic signals.Type: GrantFiled: October 31, 1986Date of Patent: October 4, 1994Assignees: Board of Regents, The University of Texas System, Monsanto CompanyInventors: Darrell H. Carney, Kevin C. Glenn
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Patent number: 5340735Abstract: Mutant B. lentus DSM 5483 proteases are derived by the replacement of at least one amino acid residue of the mature form of the B. lentus DSM 5483 alkaline protease. The mutant proteases are expressed by genes which are mutated by site-specific mutagenesis. The amino acid sites selected for replacement are identified by means of a computer based method which compares the three dimensional structure of the wild-type protease and a reference protease.Type: GrantFiled: May 29, 1991Date of Patent: August 23, 1994Assignee: COGNIS, Inc.Inventors: Teresa Christianson, Dean Goddette, Beth F. Ladin, Maria R. Lau, Christian Paech, Robert B. Reynolds, Charles R. Wilson, Shiow-Shong Yang
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Patent number: 5324648Abstract: Substituted isocoumarins, their use in inhibiting serine proteases with trypsin-like, chymotrypsin-like and elastase-like specificity and their roles as anti-inflammatory agents.Type: GrantFiled: June 17, 1992Date of Patent: June 28, 1994Assignee: Georgia Tech Research CorporationInventors: James C. Powers, Chih-Min Kam, Josef Oleksyszyn, J. A. Glinski, M. A. Hernandez
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Patent number: 5298401Abstract: In a process for the quantitative determination of the function and antigenic concentration of a substance contained in a biological liquid, the substance is immobilized, the function is determined by the addition of a specific substrate which is then removed by washing, and in a subsequent step the immunological concentration of the bound substance is determined using an appropriate specific detector system with or without the use of an antibody.Type: GrantFiled: January 5, 1989Date of Patent: March 29, 1994Inventor: Bernd Binder
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Patent number: 5242810Abstract: The present invention relates to novel, bifunctional inhibitors of both platelet activation and thrombin. These bifunctional inhibitors are characterized by two domains -- a glycoprotein IIb/IIIa inhibitory domain and a thrombin inhibitory domain. The invention also relates to DNA sequences which encode the bifunctional inhibitors of this invention, recombinant DNA molecules which contain these DNA sequences and host transformed with these DNA molecules. The invention further relates to he recombinant expression of the bifunctional inhibitors of this invention by transformed hosts as well as to methods for purifying such recombinant bifunctional inhibitors. This invention also provides compositions and methods employing the novel bifunctional inhibitors alone or together with a fibrinolytic agent.Type: GrantFiled: December 7, 1990Date of Patent: September 7, 1993Assignee: Biogen, Inc.Inventors: John M. Maraganore, Betty H. Chao, Kathryn L. Strauch, Jeffrey S. Thompson
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Patent number: 5218137Abstract: Light activated acyl-enzymes of the formula: ##STR1## are disclosed. In the compounds of Formula (III), ENZ is an enzyme, X is O or S, Y is --NR.sub.3 R.sub.4, --OR.sub.5, or --SR.sub.5, and Z is a nucleophile. m is 0 to 3 and n is 1 or 2. Y is substituted on the ring at either or both of the 4 and 6 position.R.sub.1 and R.sub.2 are each independently H, C1 to C4 alkyl, C3 to C4 unconjugated alkenyl, or C3 to C4 unconjugated alkynyl.R.sub.3 and R.sub.4 are each independently H, C1 to C4 alkyl, C3 to C4 unconjugated alkenyl, or C3 to C4 unconjugated alkynyl, except that R.sub.3 and R.sub.4 are not simultaneously both H. R.sub.5 is C1 to C4 alkyl, C3 to C4 unconjugated alkenyl, or C3 to C4 unconjugated alkynyl.Methods of using the acyl-enzymes and intermediates for making the acyl-enzymes are disclosed.Type: GrantFiled: March 25, 1992Date of Patent: June 8, 1993Assignee: Duke UniversityInventors: Ned A. Porter, John D. Bruhnke
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Patent number: 5214033Abstract: Fragments of the factor VIII:C polypeptide have been discovered which exhibit highly specific factor VIII activity. Monoclonal antibodies to the polypeptide fragments and methods for the isolation and purification of said fragments are also disclosed.Type: GrantFiled: July 15, 1991Date of Patent: May 25, 1993Assignee: Scripps Clinic & Research FoundationInventors: Theodore S. Zimmerman, Carol A. Fulcher
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Patent number: 5151355Abstract: A liquid thrombin preparation is prepared by reacting a unit of prothrombin with less than 5 units of thromboplastin in the presence of calcium, contacting the resultant thrombin with a phosphate buffer, and diluting and filtering the suspension. The filtrate is then applied sequentially to an anion-exchange agarose column and a cation-exchange agarose column and the thrombin fraction is step-wise eluted from the latter column with phosphate buffered saline. Liquid thrombin preparations thereby obtained have specific activities greater than 1,600 U/mg and can be used in haemostasis.Type: GrantFiled: January 23, 1991Date of Patent: September 29, 1992Assignee: Warner Lambert Pottery Road LimitedInventors: Carmel Crowley, Timothy G. Sheehan, Frederick G. Ward
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Patent number: 5149533Abstract: Tissue plasminogen activator analogs exhibiting greater specificity for fibrin than native t-PA are disclosed. The analogs include the K1 domain of native t-PA replaced with another kringle domain mediating the binding of the analog to fibrin. The kringle contains six cysteine residues. The t-PA analogs may further include a variety of substitutions and modifications. Pharmaceutical compositions containing one or more of the t-PA analogs along with a physiologically acceptable carrier or diluent are also disclosed.Type: GrantFiled: August 12, 1991Date of Patent: September 22, 1992Assignee: ZymoGenetics, Inc.Inventors: Eileen R. Mulvihill, Shinji Yoshitake, Yasunori Ikeda, Suguru Suzuki, Akira Hashimoto, Teruaki Yuzuriha, Bjorn A. Nexo
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Patent number: 5143838Abstract: A method of producing thrombin from Factor II (prothrombin) comprising the steps of:a) applying a solution of citrated plasma or citrated plasma fraction containing Factor II onto an equilibrated anion exchanger to bind Factor II thereto;b) applying a solution containing calcium ions to the exchanger to convert the Factor II to thrombin, andc) selectively eluting the thrombin from the carrier.Type: GrantFiled: December 20, 1989Date of Patent: September 1, 1992Assignee: Biotest Pharma GmbHInventors: Michael Kraus, Wolfgang Moller
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Patent number: 5130244Abstract: A stable aqueous thrombin solution containing thrombin and a sugar and an amino acid as a stabilizer is disclosed. According to the present invention, there is provided a stable aqueous thrombin solution.Type: GrantFiled: August 5, 1988Date of Patent: July 14, 1992Assignee: The Green Cross CorporationInventors: Hideo Nishimaki, Kenmi Miyano, Shouju Kameyama, Kazuo Takechi, Yoshiro Iga
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Patent number: 5114851Abstract: Light activated acyl-enzymes of the formula: ##STR1## are disclosed. In the compounds of Formula (III), ENZ is an enzyme, X is O or S, Y is --NR.sub.3 R.sub.4, --OR.sub.5, or --SR.sub.5, and Z is a nucleophile. m is 0 to 3 and n is 1 or 2. Y is substituted on the ring at either or both of the 4 and 6 position.R.sub.1 and R.sub.2 are each independently H, C1 to C4 alkyl, C3 to C4 unconjugated alkenyl, or C3 to C4 unconjugated alkynyl.R.sub.3 and R.sub.4 are each independently H, C1 to C4 alkyl, C3 to C4 unconjugated alkenyl, or C3 to C4 unconjugated alkynyl, except that R.sub.3 and R.sub.4 are not simultaneously both H. R.sub.5 is C1 to C4 alkyl, C3 to C4 unconjugated alkenyl, or C3 to C4 unconjugated alkynyl.Methods of using the acyl-enzymes and intermediates for making the acyl-enzymes are disclosed.Type: GrantFiled: August 29, 1989Date of Patent: May 19, 1992Assignee: Duke UniversityInventors: Ned A. Porter, John D. Bruhnke
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Patent number: 5102995Abstract: A modified heparin cofactor II is disclosed, HCII (Leu.sub.444 .fwdarw.Arg), which has substantially improved inhibitory activity against thrombin compared to native HCII or antithrombin.Type: GrantFiled: October 20, 1989Date of Patent: April 7, 1992Assignee: Washington UniversityInventors: Douglas M. Tollefsen, Vivianna M. Derechin, Morey A. Blinder
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Patent number: 5059525Abstract: The present invention provides a dry reagent for blood coagulation tests in which an at least partial course of the coagulation cascade takes place, comprising a carrier material which contains a chromophoric substrate of a protease of the blood coagulation system, at least one factor and/or co-factor of the blood coagulation system and a buffer.Type: GrantFiled: May 29, 1990Date of Patent: October 22, 1991Assignee: Boehringer Mannheim GmbHInventors: Knut Bartl, Udo Becker, Helmut Lill, Hans Wielinger
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Patent number: 5045315Abstract: 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: October 23, 1990Date of Patent: September 3, 1991Assignee: American Home Products CorporationInventors: Paul P. Hung, Narender K. Kalyan, Shaw-guang L. Lee
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Patent number: 4965203Abstract: Improved thrombin formulations, stable at room temperature using stabilizing quantities of a polyol and a buffer at specific pHs are described wherein crude thrombin is first purified by two-stage ion exchange chromatography.Type: GrantFiled: June 13, 1989Date of Patent: October 23, 1990Assignee: Warner-Lambert CompanyInventors: Steven B. Silbering, Rowland P. Blythe, Jr., Russell U. Nesbitt, Jr., Mahdi B. Fawzi
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Patent number: 4945054Abstract: 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: GrantFiled: May 17, 1983Date of Patent: July 31, 1990Assignee: Commissariat a l'Energie AtomiqueInventors: Christine Fougnot, Marcel Jozefowicz, Robert D. Rosenberg
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Patent number: 4710459Abstract: The present invention provides a process for the determination of fibrin monomer in plasma, wherein a plasma sample containing fibrin monomer and freed from plasmin inhibitors is incubated in buffered solution with tissue plasminogen activator (EPA), plasminogen and a chromogenic plasmin substrate and the color formed is measured as a measure of the amount of fibrin monomer.The present invention also provides a reagent for the determination of fibrin monomer in plasma, wherein it contains plasminogen, tissue plasminogen activator (EPA), chromogenic plasmin substrate and buffer (pH 7.0 to 9.0).Type: GrantFiled: August 21, 1985Date of Patent: December 1, 1987Assignee: Boehringer Mannheim GmbHInventors: Knut Bartl, Helmut Lill
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Patent number: 4668621Abstract: Assays and reagents for the direct determination of blood factors, as well as complementary methods and reagents for determining such blood factors and haptens, antigens and receptors. The methods involve clot formation due to thrombin activated fibrin formation from insolubilized fibrogen and labeled solubilized fibrogen. Insolubilized label can be determined prior to or after clot formation.Type: GrantFiled: April 22, 1985Date of Patent: May 26, 1987Assignee: Wake Forest UniversityInventor: George J. Doellgast
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Patent number: 4495278Abstract: Viruses, particularly hepatitis viruses, in blood clotting enzyme compositions are inactivated with little enzyme activity loss by heating the compositions in the dry state. The novel products which result are therapeutically and diagnostically useful.Type: GrantFiled: April 27, 1981Date of Patent: January 22, 1985Assignee: Baxter Travenol Laboratories, Inc.Inventor: William R. Thomas
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Patent number: 4480030Abstract: A process for quantitatively assaying factor Xa from a medium by reacting the medium with tripeptide derivatives having the formula ##STR1## wherein R.sup.5 is a chromogenic substituted amino group capable of being split off by enzymatic hydrolysis to form a colored or fluorescent product H--R.sup.5. The quantity of split product H--R.sup.5 released by the enzymatic action on the tripeptide derivative is determined photometrically, spectrophotometrically, fluorescence-spectrophotometrically, or electrochemically. The quantity of released split product H--R.sup.5 per time unit is proportional to the quantity of enzyme present in the starting material.Type: GrantFiled: September 15, 1982Date of Patent: October 30, 1984Assignee: Pentapharm A.G.Inventor: Lars G. Svendsen
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Patent number: 4374830Abstract: Novel hemostatic agent comprises equine arterial fibrillar collagen in a carrier. The agent is useful for the aggregation of platelets for clinical diagnostic tests and for the clotting of blood, such as for controlling bleeding in warm blooded species. The fibrillar collagen is obtained by extracting homogenized equine arterial tissue with aqueous solutions followed by extensive dialysis.Type: GrantFiled: August 12, 1981Date of Patent: February 22, 1983Assignee: Research Corp.Inventor: Morris D. Schneider
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Patent number: 4363319Abstract: A prepackaged coagulant composition and method of preparing same has been devised for use in direct or topical application to wounds so as to cause superficial clotting in which thrombin is combined with special preservatives and a saline solution. A ready-to-use bandage is saturated with the resultant solution, sealed and stored so as not to lose its reactive properties with the fibrinogen in the blood when applied to a wound or cut.Type: GrantFiled: April 20, 1981Date of Patent: December 14, 1982Assignee: Applied Medical Devices, Inc.Inventor: John H. Altshuler
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Patent number: 4347243Abstract: Acid soluble, pepsin resistant, platelet aggregating material isolated from equine arterial tissue by extraction with dilute aqueous acid, method of isolation and use to control bleeding.Type: GrantFiled: August 12, 1981Date of Patent: August 31, 1982Assignee: Research CorporationInventor: Morris D. Schneider
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Patent number: 4303592Abstract: A new compound amidinophenylmethylsulfonylfluoride is formed and preferably used in the para isomer form as an irreversible inactivator of selected serine proteases.Type: GrantFiled: January 9, 1980Date of Patent: December 1, 1981Assignee: Center for Blood Research, Inc.Inventors: Richard Laura, David H. Bing
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Patent number: 4286056Abstract: This is an improved method for producing activated prothrombin complex concentrate which comprises controlling the degree of activation by determining the activation state of the starting material and then varying at least one of the activation conditions in accordance with analyses of the progress of activation of the starting material to arrive at a predetermined activation level.Type: GrantFiled: January 28, 1980Date of Patent: August 25, 1981Assignee: Baxter Travenol Laboratories, Inc.Inventors: Thomas J. Andary, L. Raymond Berkebile, William R. Thomas, Daphne C. Tse