Coagulant Patents (Class 514/834)
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Patent number: 6130203Abstract: Hybrid proteins which affect blood coagulation comprise a region from a donor anticoagulant or antithrombotic protein, and the resulting hybrid protein has a modified biological activity. Information concerning the hybrid proteins implicates DNA sequences encoding the proteins and hosts, including transgenic animals, that possess these DNA sequences; antibodies directed against hybrid proteins; methods of modifying the properties of proteins; and treatment methods employing hybrid proteins.Type: GrantFiled: February 3, 1999Date of Patent: October 10, 2000Assignee: Baxter AktiengesellschaftInventor: Johannes J. Voorberg
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Patent number: 6110483Abstract: The adherent coating of the invention comprises a stabilizing polymer together with an active agent (a hydrophilic polymer and/or a bioactive agent) in a layer bonded to the surface of a medical device. This invention encompasses the coating liquids used for coating medical devices, methods of coating the devices, and the coated devices. The stabilizing polymer is selected to entrap the active agent in a coating that has a high degree of flexibility and has improved bonding to a wide variety of substrates. Preferred stabilizing polymers are cross-linkable acrylic and methacrylic polymers, ethylene acrylic acid copolymers, styrene acrylic copolymers, vinyl acetate polymers and copolymers, vinyl acetal polymers and copolymers, epoxy, melamine, other amino resins, phenolic polymers, copolymers thereof, and combinations.Type: GrantFiled: June 23, 1997Date of Patent: August 29, 2000Assignee: STS Biopolymers, Inc.Inventors: Richard J. Whitbourne, Xianping Zhang
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Patent number: 6048720Abstract: Processes for improving the in vivo function of factor VIII by shielding exposed targets of the factor VIII comprise a) immobilizing the factor VIII by interaction with a group-specific adsorbent carrying ligands manufactured by organic-chemical synthesis, for preventing polymer coupling to reactive amino acids of the immobilized factor VIII, within or adjacent to interaction domains; b) activating a biocompatible polymer; c) conjugating the activated biocompatible polymer to external sites of the immobilized factor VIII; and thereafter d) eluting the conjugate from the adsorbent. Processes for administering factor VIII comprise subcutaneously, intramuscularly, intradermally or intravenously administering a conjugate of factor VIII and a biocompatible polymer, and methods for treatment of hemophilia A comprise subcutaneous, intramuscular, intradermal or intravenous administration of a conjugate of factor VIII and a biocompatible polymer.Type: GrantFiled: May 21, 1998Date of Patent: April 11, 2000Assignee: Pharmacia & Upjohn ABInventors: Johanna Dalborg, Helena Sandberg, Anna-Lisa Smeds, Eva kerblom
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Patent number: 6037366Abstract: A composition including 2-hexyl cyanoacrylate and gold is useful in treating arteriovenous malformations (AVMs) and other body lumens to be blocked.Type: GrantFiled: September 11, 1998Date of Patent: March 14, 2000Assignee: Prohold Medical Technologies, Inc.Inventors: Robert E. Krall, Charles W. Kerber, Kimberly Knox
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Patent number: 6013620Abstract: The invention relates to a pharmaceutical composition for the treatment of patients with blood coagulation diseases which are caused by coagulation factor deficiency and/or inhibitors of coagulation factors, whereby the composition as a FEIB-activity and is characterized in that it has Factor VIIa and at least one further active ingredient and the activity of at least 10 Factor VIIa units per unit FEIBA. Additionally, the invention comprises a method for the production of the pharmaceutical preparation and its use.Type: GrantFiled: September 11, 1997Date of Patent: January 11, 2000Assignee: Baxter AktiengesellschaftInventors: Peter Turecek, Hans-Peter Schwarz, Gerda Redl
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Patent number: 5919766Abstract: The present invention relates to a novel composition comprising coagulation Factor VIII and a non-ionic surfactant such as block co-polymers, e.g. polyoxamers or polyoxyethylene (20) fatty acid esters e.g. polysorbate 20 or polysorbate 80 as a stabilizer. The composition can also comprise sodium chloride, calcium chloride, L-histidine and/or sugars or sugar alcohols.Type: GrantFiled: May 27, 1997Date of Patent: July 6, 1999Assignee: Pharmacia & Upjohn AktiebolagInventors: Thomas Osterberg, Angelica Fatouros
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Patent number: 5919908Abstract: A final drug product comprises a plasma protein selected from the group consisting of coagulation factor VIII and factor IX, in an aqueous solution. The concentration of oxygen in the solution is reduced and/or the solution contains an antioxidant. The solution further contains a carbohydrate in a concentration of at least 350 mg/ml. The protein activity after storage for at least 6 months at a temperature of from 0.degree. C. to 40.degree. C. is from 70% to 130% of its initial value. In a process for preparing the final drug product and a method for improving the long-term stability of coagulation factor VIII or factor IX in an aqueous solution, a carbohydrate is included in the solution in a concentration of at least 350 mg/ml and the solution is stored in its final container under an oxygen-reduced atmosphere or includes an antioxidant.Type: GrantFiled: November 26, 1997Date of Patent: July 6, 1999Assignee: Pharmacia & Upjohn ABInventors: Thomas Osterberg, Angelica Fatouros
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Patent number: 5914098Abstract: The present invention relates to an aerosol composition for forming a preferably hydrated membrane which after vaporizing comprises as least one hydrophobic phase containing at least one film-forming polymer at least partly solubilized in an organic solvent system. The polymer is selected from hydrophobic polyaminoacids, preferably from the polyaminoacids obtained from at least one of the amino acids alanine, valine, leucine, isoleucine, proline, methionine, phenylalanine, tryptophan, aspartic and glutamic acid esters, or the derivatives thereof. The compositions also comprises as least one hydrophilic phase, and at least one propellant. The preferably hydrated membrane formed by vaporizing this composition, the application of the composition and of the preferably hydrated membrane as a dressing, are also disclosed.Type: GrantFiled: May 10, 1996Date of Patent: June 22, 1999Assignee: Flamel TechnologiesInventors: Gerard Soula, Jean-Michel Grosselin, Rafael Jorda, Catherine Castan
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Patent number: 5910481Abstract: Hybrid proteins which affect blood coagulation comprise a region from a donor anticoagulant or antithrombotic protein, and the resulting hybrid protein has a modified biological activity. Information concerning the hybrid proteins implicates DNA sequences encoding the proteins and hosts, including transgenic animals, that possess these DNA sequences; antibodies directed against hybrid proteins; methods of modifying the properties of proteins; and treatment methods employing hybrid proteins.Type: GrantFiled: November 13, 1995Date of Patent: June 8, 1999Assignee: Immuno AGInventor: Johannes J. Voorberg
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Patent number: 5897860Abstract: The present invention relates to a hemostatic composition comprising at least 0.1 NIH U/ml of thrombin, about 0.01 mU/ml of casein kinase II, and from 10 ng/ml to 100 ng/ml of sphingosine or a sphingosine derivative. The composition is effective in treating patients suffering from hemophilia, ulcers, or microbial infections. In addition, the composition is effective in reducing clotting time during the surgical procedure of suturing blood vessels.Type: GrantFiled: September 30, 1996Date of Patent: April 27, 1999Assignee: Korea Institute of Science TechnologyInventors: Seung-Ho Kim, Jin Young Lee, Moon Hi Han
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Patent number: 5891843Abstract: The invention relates to a pharmaceutical composition for the treatment of patients with blood coagulation diseases which are caused by coagulation factor deficiency and/or inhibitors of coagulation factors, whereby the composition has a FEIB-activity and is characterized in that it has Factor VIIa and at least one further active ingredient and the activity of at least 10 Factor VIIa units per unit FEIBA. Additionally, the invention comprises a method for the production of the pharmaceutical preparation and its use.Type: GrantFiled: August 22, 1996Date of Patent: April 6, 1999Assignee: Immuno AktiengesllschaftInventors: Peter Turecek, Hans-Peter Schwarz, Gerda Redl
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Patent number: 5888974Abstract: A hybrid procoagulant factor VIII is produced by isolation and recombination of human and other nonhuman mammalian factor VIII subunits or domains, or by genetic engineering of the human and animal factor VIII genes. Subunits or domains of factor VIII that have been purified from human or animal plasma are isolated, and hybrid human/animal factor VIII is produced by (1) mixing either animal heavy chain subunits with human light chain subunits or by mixing human heavy chain subunits with animal light chain subunits, thereby producing human light chain/animal heavy chain and human heavy chain/animal light chain hybrid molecules; or by (2) mixing one or more domains of one species with one or more domains of the other species. These hybrid molecules are isolated by ion exchange chromatography.Type: GrantFiled: June 7, 1995Date of Patent: March 30, 1999Assignee: Emory UniversityInventors: John S. Lollar, Marschall S. Runge
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Patent number: 5846567Abstract: A method, composition and kit for effecting hemostasis of a bleeding point and/or dissociating an adherent blood clot at a lesion site on an internal organ, include a composition comprising hydrogen peroxide and surfactant. The composition is applied to the site thereby effecting hemostasis and clot dissociation and clearing the field for endoscopy.Type: GrantFiled: April 16, 1997Date of Patent: December 8, 1998Assignee: Chek-Med Systems, Inc.Inventors: Anthony N. Kalloo, Pankaj Jay Pasricha
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Patent number: 5837679Abstract: Analogs of blood factors which are transiently inactive are useful in treatment of diseases characterized by thrombosis. In addition, modified forms of activated blood factors that generate the active blood factor in serum but have extended half-lives are useful in treating hemophilic conditions. These modified forms of the blood factor may be acylated forms which are slowly deacylated in vivo.Type: GrantFiled: June 6, 1995Date of Patent: November 17, 1998Assignee: COR Therapeutics, Inc.Inventors: David L. Wolf, Uma Sinha
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Patent number: 5830467Abstract: A pharmaceutical preparation contains protein C and a thrombolytically active substance that does not activate protein C. This preparation prevents reocclusion usually occurring in the course of thrombolysis therapy.Type: GrantFiled: June 1, 1995Date of Patent: November 3, 1998Assignee: Immuno AktiengesellschaftInventors: Johann Eibl, Anton Philapitsch, Hans Peter Schwarz
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Patent number: 5733873Abstract: A composition comprising coagulation factor VIII and a non-ionic surfactant such as block copolymers, e.g., polyoxamers or polyoxyethylene (20) sorbitan fatty acid esters, e.g., polysorbate 20 or polysorbate 80 as stabilizer is provided. The composition can also comprise sodium chloride, calcium chloride, L-histidine and/or sugars or sugar alcohols.Type: GrantFiled: May 20, 1994Date of Patent: March 31, 1998Assignee: Pharmacia & Upjohn ABInventors: Thomas Osterberg, Angelica Fatouros
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Patent number: 5726028Abstract: The present invention relates to a method for detecting disturbances of the protein C/protein S system.Type: GrantFiled: August 4, 1995Date of Patent: March 10, 1998Assignee: Behring Diagnostics GmbHInventor: Michael Kraus
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Patent number: 5716795Abstract: The present invention provides a one-stage assay which uses soluble thrombomodulin for directly determining the functional status in plasma of the protein C system. The activity of the protein C system is used to determine the risk of thrombosis in the host individual. Alternatively, the activity of the protein C system is used to determine the presence of a malignant cancer and other pathologies. In another embodiment of the invention, a heparin adsorbent step is added to the assay process which reveals the existence of an additional component in protein C activation, and thus the existence of an additional component in the regulation of blood coagulation.Type: GrantFiled: January 3, 1996Date of Patent: February 10, 1998Inventor: John T. Matschiner
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Patent number: 5643739Abstract: An improved assay for determining sensitivity to activated protein C in test samples has been developed to ensure rapid and accurate evaluations. This assay is based on measuring the conversion, by activated factor VIII within a test sample, of added factor X to an activated form. The activated protein C sensitivity of the test sample is determined by the relative inhibition of factor X conversion as compared to a control. A test sample that has decreased sensitivity to activated protein C will show relatively low inhibition, and vice versa.Type: GrantFiled: May 1, 1995Date of Patent: July 1, 1997Assignee: Immuno AGInventors: Katalin Varadi, Hans Peter Schwarz, Hartmut Lang, Berta Moritz
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Patent number: 5593968Abstract: A virus-inactivated Factor-Xa preparation with at least 100 units coagulation factor activity per mg protein is described, wherein this preparation is produced by activation of a corresponding starting material and subsequent treatment for the inactivation of infectious agents, particularly viruses. By incubation, the preparation obtained in this manner is transformed into a stable beta-Factor Xa preparation. In addition, the use of the present preparation for the treatment of hemophilia A inhibitor patients is disclosed.Type: GrantFiled: August 2, 1994Date of Patent: January 14, 1997Assignee: Immuno AktiengesellschaftInventors: Peter Turecek, Eibl Johann, Hans-Peter Schwarz
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Patent number: 5576291Abstract: Stabilized and activated Factor VIII is used as a therapeutic agent to treat patients with a Factor VIII deficiency. This includes hemophilia A patients as well as patients with Factor VIII inhibitors which block the hemostatic activity of Factor VIII. The stabilized and activated Factor VIII is also prepared in a therapeutic composition with a therapeutically acceptable adjuvant.Type: GrantFiled: September 13, 1993Date of Patent: November 19, 1996Assignee: Baxter International Inc.Inventors: Joseph E. Curtis, Sam L. Helgerson, Roger L. Lundblad, Shu-Len Liu
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Patent number: 5552296Abstract: In a method for the determination of coagulation parameters in sample material via a reaction cascade in which a thrombin-catalyzed formation of a fibrin clot from fibrin monomers occurs and the formation of the fibrin clot is measured, an inhibitor of F XIII is added. By this means the reaction vessel can be used several times for coagulation tests.Type: GrantFiled: January 30, 1995Date of Patent: September 3, 1996Assignee: Boehringer Mannheim GmbHInventors: Enno Adema, Ulrike Gebert, Reinhard Herz
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Patent number: 5550028Abstract: The compound 2,3,5,6-tetrahydroxy-1,4-quinone, its derivatives and structural analogs are used as activators for intrinsic blood coagulation and as diagnostic reagents for the activated partial thromboplastin time test of blood coagulation.Type: GrantFiled: June 7, 1995Date of Patent: August 27, 1996Assignee: Dade International Inc.Inventors: Ted C. K. Lee, Franz H. Pelzer, Leslie A. Motley
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Patent number: 5525334Abstract: Proposed is a method for vascular embolization of the blood vessel of a patient by introducing an aqueous solution of a specific thermosensitive polymer, which is liquid at low temperatures but causes coagulation when heated up to the body temperature of the patient, into the blood vessel followed by in situ heating of the solution. The thermosensitive polymer found to be suitable for the purpose is a homopolymer or copolymer of an N-substituted (meth) acrylamide monomer having a specified intrinsic viscosity in tetrahydrofuran and gives an aqueous solution capable of exhibiting phase transition from a liquid to a coagulate at a transition temperature of 10.degree. to 37.degree..Type: GrantFiled: March 22, 1995Date of Patent: June 11, 1996Assignee: Japan as represented by Director General of Agency of Industrial Science and TechnologyInventors: Shoji Ito, Yuji Matsumaru, Takashi Hirano, Shinichi Ohashi
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Patent number: 5447720Abstract: A composition and method of treatment of hemoglobinopathies, such as, for example, sickle cell disease and thalassemia, wherein an inventive extract used in such treatment is obtained from alfalfa and other certain plant materials, preferably using a hydroxide base and hexane. In the most preferred embodiment, the plant material is first extracted with 1,1,1-trichloroethane and a hydroxide base, followed by extraction with hexane. The polar acidic compounds present in alfalfa and other plant materials selectively dissolve in the hexane phase and exhibit good antisickling activity in vitro. Further, these active compounds which comprise the inventive extract are effective in vivo by significantly alleviating the many clinical manifestations of sickle cell disease and thalassemia experienced by the affected patients.Type: GrantFiled: July 6, 1993Date of Patent: September 5, 1995Assignee: Sunday O. FaduluInventor: Sunday O. Fadulu
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Patent number: 5366869Abstract: A multiple coagulation test device has a plurality of tubes, each tube having associated coagulation detection means, and containing a treatment dosage of a coagulation enhancing agent. Whole blood samples are placed in the tubes which are mixed and warmed to 37.degree. C., with the time to coagulation determined. The agent giving the lowest clotting time is selected as the most effective treatment for reducing hemorrhaging within a few minutes and the selected treatment begun. Utilizing the inventive device eliminates the need to use a multiple agent approach, by identifying the most effective course of action.Type: GrantFiled: November 8, 1991Date of Patent: November 22, 1994Inventor: Sheldon Goldstein
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Patent number: 5321133Abstract: The invention relates to sulphated polysaccharides obtained from fucuses extracted from pheophyceae. The molecular weight of these polysaccharides is greater than 5 and less than 40 Kda; their sulphur content is greater than that of the original fucus and they contain less than 0.15% of contaminant proteins. Applications as anticoagulant and anticomplementary agents.Type: GrantFiled: January 16, 1992Date of Patent: June 14, 1994Assignee: Institut Francais de Recherche pour l'Exploitation de la Mer-IFREMERInventors: Sylvia Colliec, Jacqueline Bretaudiere, Patrick Durand, Anne-Marie Fischer, Jacqueline Jozefonvicz, Bernard Kloareg, Catherine Vidal
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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: 5204323Abstract: The invention provides an antidote to blood anticoagulants comprising Factor VIII or fragments of Factor VIII which retain its activity or a substance which increases its concentration in blood.Type: GrantFiled: September 20, 1991Date of Patent: April 20, 1993Assignee: Ciba-Geigy CorporationInventors: Valerie S. Findlay, Roger Kerry, Graham F. Pay, Robert B. Wallis, Keith D. Butler
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Patent number: 5149540Abstract: A stable thrombin composition for oral administration having an excellent solubility is prepared with thrombin as a hemostatic ingredient, gelatin, albumin and glycine as a stabilizer and sucrose and/or sugar alcohol as a carrier. The thrombin composition is effective for the treatment of hemorrhage in the upper alimentary canal, is stable even at room temperature conditions for long periods of time, has excellent solubility and can be orally administered in a simple manner.Type: GrantFiled: February 27, 1991Date of Patent: September 22, 1992Assignee: Mochida Pharmaceutical Co., Ltd.Inventors: Yasuyuki Kunihiro, Ryo Tanaka, Seishichi Hata, Koji Yamada
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Patent number: 5101016Abstract: Polypeptides have been discovered which exhibit high specific VIII:C coagulant activity. Monoclonal antibodies to the polypeptides are also disclosed.Type: GrantFiled: October 10, 1990Date of Patent: March 31, 1992Assignee: Scripps Clinic and Research FoundationInventors: Theodore S. Zimmerman, Carol A. Fulcher
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Patent number: 4857635Abstract: Polypeptides have been discovered which exhibit high specific VIII:C coagulant activity. Monoclonal antibodies to the polypeptides are also disclosed.Type: GrantFiled: September 20, 1985Date of Patent: August 15, 1989Assignee: Scripps Clinic and Research FoundationInventors: Theodore S. Zimmerman, Carol A. Fulcher
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Patent number: 4851450Abstract: The present invention is a group of biologically active agents, di-hydroxy alkyl glycerols with vicinal hydroxyl groups and their acetyl-derivatives having the general formula: ##STR1## where R is selected from the group of H and CH.sub.3 CO-- and x+y is between 9 and 21; and methods for their synthesis. The compounds of the present invention are synthesized starting with an unsaturated 1-O-alkyl-glycerol of the formula: ##STR2## where R is an unsaturated alkyl group with a chain length of 12 to 24 carbon atoms and introducing a vicinal hydroxyl into the alkyl carbon chain using either osmium tetroxide or performic acid, produced by mixing formic acid with hydrogen peroxide.The new glycerol ether derivatives exert platelet activating factor (PAF)-like action in vitro in low concentrations, and, surprisingly, in higher doses act as selective antagonists of PAF, or 1-O-alkyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), activities.Type: GrantFiled: October 26, 1987Date of Patent: July 25, 1989Inventor: Constantine A. Demopoulos
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Patent number: 4831119Abstract: A preparation for the treatment of hemophilia A inhibitor patients contains a protein or peptide having a specific Factor VIII:CAg activity of at least 0.5, preferably at least 1 VIII:CAg unit per mg protein, the ratio between the VIII:CAg activity and the VIII:C procoagulant activity being greater than 5:1, preferably greater than 10:1. A fragment of Factor VI-II:C, which displays a doublet of a molecular weight of 80/77 kD in electrophoresis, is reactive hemophilia A inhibitor antibodies and has VIII:CAg activity. This fragment and more low-molecular fragments of Factor VIII:C are capable of neutralizing the coagulation inhibiting effect of all tested antibodies. Such fragments can therefore be used as active component in preparations for providing immunotolerance towards Factor VIII:C in high-dose treatment of inhibitor patients. The peptides are moreover useful as an immunosorbent in specific extracorporeal adsorption treatment of inhibitor patients. The inhibitor reactive peptides can e.g.Type: GrantFiled: June 20, 1986Date of Patent: May 16, 1989Inventors: Ole Nordfang, Mirella E. Rasmussen
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Patent number: 4739039Abstract: An improved method of recovering antihemophilic factor (AHF) from cryoprecipitated blood plasma is provided. The improved method incorporates the addition of a calcium ion source during the step of cold precipitation of fibrinogen and fibronectin contaminants, as well as the addition of polyethylene glycol (PEG) at one of various stages of the recovery process. PEG may be added during the cold precipitation of fibrinogen and fibronectin, during the precipitation of AHF, or prior to the filtration of AHF solution. The method of the present invention results in a final AHF product having greatly increased solubility, higher specific activity, and lower fibrinogen and fibronectin content.Type: GrantFiled: July 15, 1987Date of Patent: April 19, 1988Assignee: Baxter Travenol Laboratories, Inc.Inventors: Rodolfo A. Vasquez, Maria E. Co-Sarno, Clifford R. Graf
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Patent number: 4735969Abstract: A novel bisulfite adduct of menadione, the menadione choline bisulfite adduct, a process for its preparation, and its use as an antihemorrhagic agent.Type: GrantFiled: November 18, 1985Date of Patent: April 5, 1988Assignee: BASF AktiengesellschaftInventors: Joachim U. Schneider, Hans Kiefer
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Patent number: 4683291Abstract: Peptides of the general formulaH.sub.2 N-(Ch)-Arg-Gly-Asp-(Cx)-Hand the derivatives thereof described herein, wherein (Cx) and (Ch) each contains 1 to 20 amino acid residues and (Ch) contains at least one Lys or Arg residue, or at least one of each, inhibit platelet-fibrinogen binding and platelet-platelet aggregation and are thus useful inhibitors of cell adhesion.Type: GrantFiled: October 28, 1985Date of Patent: July 28, 1987Assignee: Scripps Clinic and Research FoundationInventors: Theodore S. Zimmerman, Zaverio M. Ruggeri, Richard Houghten
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Patent number: 4670543Abstract: The invention relates to a process for producing FVIII/vWF complexes for therapeutical use possessing both haemophilic A activity and Willebrand activity as well as a high degree of purity, such process substantially comprising the steps of fixing the FVIII/vWF complex in physiological conditions on a particular monoclonal antibody and releasing said complex by means of a suitable elution medium having no effct on the functions of the FVIII/vWF complex but able to dissociate the bonds linking the selected monoclonal anitbody to the FVIII/vWF complex, then collecting the latter in a highly purified form.Type: GrantFiled: September 18, 1985Date of Patent: June 2, 1987Assignee: ImmunotechInventors: Alain Bourgois, Marylene Delezay, Vincent Fert