Abstract: Lipid-enveloped viruses present in purified biologically active protein products obtained from blood or cell culture systems can be inactivated by contacting the products with caprylic acid at a non-ionized concentration, pH, temperature and ionic environment sufficient to inactivate the viruses without adversely precipitating or affecting the biological activity of the protein products.
Abstract: A monoclonal antibody which is specific to human protein C which has calcium bound at the gammacarboxyglutamic acid(Gla) domain and does not recognize human protein C which is not bound to calcium at the Gla domain. The monoclonal antibody is used in an immunoassay method for determining human protein C having a Gla domain and in a method for recovering human protein C having a Gal domain.
Abstract: To maintain an almost unchanged plasma-protein profile in a patient subsequent to plasma exchange, the plasma-exchange medium contains the most essential human serum proteins, except for the coagulation factors, at a concentration of 75 g/l.
Abstract: This invention relates to a process and to absorbent material for isolating coagulation factors, including FVIII and vWF, from the example blood plasma and plasma products by means of liquid chromatography. The adsorbent material comprises a polymeric carrier to which amino groups are linked as ligands through spacers. The spacers have a chain length of at least 6 atoms and contain at least one hydrophilic link within the chain. The spacers preferably have the formula --(CH.sub.2).sub.m --CO--NH--(CH.sub.2).sub.n -- wherein m and n each represent an integer of 1-6 and m+n is at least 4. The spacers are preferably linked to the carrier through --CO--NH-- groups. The ligand density in the absorbent material is preferably higher than 30 umoles/ml of swollen matrix.
Type:
Grant
Filed:
August 3, 1988
Date of Patent:
November 28, 1989
Assignee:
Waander Riethorst
Inventors:
Waander Riethorst, Bondewyn W. Konig, Willem G. van Aken, Adriaan Bantjes, Tom Beugeling, Marcelinus P. W. M. Te Booy
Abstract: A compound of the formula: ##STR1## wherein X is a non-chromophoric bridging group which provides at least three single covalent bonds between Ring B and the group R;R is a group containing a reactive halogen atom; andeach A independently is H or an acidic group;provided that the molecule contains sufficient acidic groups to render it water soluble and then when X provides only 3 covalent bonds between Ring B and R, the latter is not a chlorodifuoropyrimidyl group, which is suitable for the preparation of a protein adsorbent or precipitant for use in the separation of mixtures of proteins.
Type:
Grant
Filed:
July 14, 1986
Date of Patent:
September 5, 1989
Assignee:
Imperial Chemical Industries PLC
Inventors:
Cecil V. Stead, Steven J. Burton, Christopher R. Lowe
Abstract: A method and composition for assaying protein C is described. The method comprises reacting a protein C-containing medium with a protein C-activating activator preparation obtained from venom of the snake Agkistrodon contortrix, or venom of another snake species which undergoes an immunological cross-reaction with the venom of Agkistrodon contortrix, to cause maximum activation of protein C and subsequently determining the quantity of activated protein C, said quantity being proportional to the amount of protein C in said medium. Also disclosed is a method and composition for treating thrombotic disorders with the activator preparation and a method of obtaining the activator preparation by culturing of a cloned microorganism.
Abstract: 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.
Abstract: 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.
Abstract: The present invention is a protein purification column comprising an organic substrate matrix having low reactivity to proteins, said matrix being capable of maintaining monoclonal antibodies attached thereto in an external configuration and preventing interaction with the protein to be bound to the antibody, and a monoclonal antibody attached to the substrate, the monoclonal antibody having a specific affinity for the protein to be isolated.The present invention also is a method for isolating and purifying specific protein from a solution, wherein1. Protein-specific monoclonal antibody is attached to the organic substrate matrix described above to form an antibody-substrate conjugate; and2. Protein to be isolated, in an appropriate buffer solution, is contacted with the antibody-substrate conjugate.An appropriate buffer may be applied to remove non-antibody bound contaminants, followed by an appropriate eluting agent to remove the protein from the monoclonal antibody.
Type:
Grant
Filed:
August 7, 1987
Date of Patent:
May 16, 1989
Assignee:
Scripps Clinic and Research Foundation
Inventors:
Theodore S. Zimmerman, Carol A. Fulcher
Abstract: A complex of a therapeutic agent is disclosed in which the therapeutic agent is complexed to an ammonium ion selected from the group consisting of ##STR1## where R.sup.1 and R.sup.2 are the same or different and are alkyl or hydroxy substituted alkyl containing 1 to 6 carbon atoms; andR, R' and R" are the same or different and are saturated or unsaturated aliphatics containing at least 10 carbon atoms, ##STR2## where R.sup.1, R.sup.2 and R" are as defined above, ##STR3## where R.sup.3 is independently alkyl or hydroxy substituted alkyl containing at least 10 carbon atoms; and R.sup.1, R.sup.2, R.sup.3 and R' having the meanings given above; and ##STR4## where R.sup.1, R.sup.2 and R.sup.3 have the meanings given above. The therapeutic agent is heparin, a biologically active peptide or protein or an antineoplastic drug. The therapeutic agent may also be covalently bonded to a triglyceride type backbone to form a compound.
Abstract: There is disclosed a method of inactivating reproductive filterable pathogens in tissue adhesives containing fibrinogen and Factor XIII, with their biologic activity being largely preserved. In order to provide a tissue adhesive preparation of human or animal origin, which exhibits a high safety with respect to reproductive filterable pathogens and whose biologic activity is largely preserved, preparations having a minimum content of 100 units of Factor XIII/g of fibrinogen are heated in the dry state in the presence of an oxygen-free inert protective gas or under vacuum.
Abstract: The invention relates to a process for the pasteurization of plasma proteins and plasma protein fractions without essentially impairing their biological activity, by subjecting a suspension of the plasma proteins or plasma protein fractions in glycerol esters of saturated or singly or multiply unsaturated fatty acids having 4-22 carbon atoms, or mixtures of these esters, as the inert heat-transfer agent, with a maximum water content of the suspension of 1% by weight, to a heat treatment at temperatures of 50.degree. to 120.degree. C.
Type:
Grant
Filed:
March 9, 1987
Date of Patent:
February 7, 1989
Assignee:
Schwab & Co Ges.m.b.H.
Inventors:
Walter Doleschel, Walter N. Doleschel, Helmut Kaltschmid
Abstract: A method of producing highly purified factor IX from crude factor IX comprising binding an A-7 monoclonal antibody to an Affigel-10 column; partially purifying the crude factor IX to produce a partially purified factor IX; applying that factor IX to the A-7-Affigel-10 column with an application buffer; washing the column with 1-3M NaCl in 0.05M Tris-HC1, 20 mM MgCl.sub.2 and 1 mM Benzamidine HCl; eluting purified factor IX from the washed column with 20 mM EDTA; and separating purified factor IX from the EDTA. An improved factor IX product produced thereby.
Abstract: Antibodies which form immune complexes with human native prothrombin only, in the presence of mixtures of human native prothrombin and human abnormal prothrombin as well as antibodies which form antibody antigen complexes with human abnormal prothrombin in the presence of such mixtures have been obtained. Immunoassay techniques are used for qualitative and quantitative determinations of these antigens in human plasma or serum. Unique methods of obtaining the antibodies are described including obtaining antibodies to native prothrombin by dissociation of antigen antibody complexes formed in the presence of calcium ions with a material having a greater affinity constant for binding with calcium ions than does prothrombin. Dissociation of the complex in this manner yields human native prothrombin antibodies which are specific and non-reactive with human abnormal prothrombin.
Type:
Grant
Filed:
October 15, 1984
Date of Patent:
September 6, 1988
Assignee:
New England Medical Center Hospitals, Inc.
Inventors:
Bruce E. Furie, Barbara C. Furie, Rita A. Blanchard
Abstract: Biological compositions are freed of functional polynucleotides by treatment of the biological composition with psoralen derivatives under irradiation conditions in which the proteins retain their original physiological activities and any polynucleotide present is rendered inactive.
Abstract: Biological compositions are decontaminated by treatment with furocoumarin derivatives and irradiation under particular conditions in which the proteins retain their original physiological activities and any pathogenic microorganisms and polynucleotide fragments thereof are rendered inactive. It has been found that reduction of the amount of dissolved oxygen in the treatment solution substantially inhibits denaturation of the proteins.
Abstract: There is provided, in accordance with practice of this invention, a process for separating Factor IX and/or Factor X from an impure protein fraction containing protein in addition to Factors IX and X. A silica resin coupled with a ligand capable of binding Factor IX and/or Factor X is provided. An aqueous solution of the impure protein fraction is applied to the ligand-coupled silica resin to thereby bind the Factor IX and/or Factor X to the resin. The Factor IX and/or Factor X is then recovered from the resin by elution.
Abstract: Compositions containing therapeutically or immunologically active proteins are rendered substantially free from infectious agents such as viable viruses and bacteria without substantial loss of therapeutic or immunologic activity by mixing the protein composition with a complex formed from transition metal ions, such as copper ions, and an angularly-fused, polynuclear heterocyclic arene having two nitrogen atoms in a "cis-ortho" relationship, such as phenanthroline, and a reducing agent such as a thiol or ascorbic acid or ascorbate salt or mixtures of ascorbic acid or ascorbate with a thiol in amounts and at a temperature and for a time sufficient to inactivate substantially all of the viruses and bacteria contained therein. Compositions containing therapeutically active proteins substantially free from viral and bacterial infectivity, which have heretofore been unattainable, can be prepared by the method of the invention.
Abstract: A method for maintaining intact, non-degraded von Willebrand factor by preventing the action of calcium activated protease(s) responsible for degradation of the factor. The action of the calcium activated protease(s) may be avoided by removing the blood platelet source of the protease(s), by filtering or centrifugal separation, or by inactivating the protease with a chelating agent removing the calcium, by a protease inhibitor, or an alkylating agent.
Type:
Grant
Filed:
May 22, 1984
Date of Patent:
December 1, 1987
Assignee:
The Blood Center of Southeastern Wisconsin
Inventors:
Thomas J. Kunicki, Robert R. Montgomery
Abstract: There is described a method of inactivating reproducible pathogens in preparations containing plasmatic enzymes and proenzymes, activated or non-activated coagulation factors, such as Factors II, V, VII, VIII, IX, X, XIII, "FEIBA", prothrombin complex preparations, plasmatic inhibitors, immunoglobulins or other blood products, such as fibronectin and fibrinogen. In order to break and overcome the protective effect of proteins on pathogens by simultaneously preserving the biological activity and the molecular integrity of the proteins, the preparation is adjusted to a salt concentration of more than 0.5 molar by the addition of ammonium sulfate and is thermally treated, whereupon the ammonium sulfate is removed from the preparation.
Abstract: Blood and proteinaceous blood products employed for their physiological and/or immunological properties are free of viable enveloped viruses by treatment with low levels of ozone, levels at which substantially all of the physiological and/or immunological activity is retained.
Abstract: Compositions containing thermally sensitive, therapeutically active proteins are pasteurized without substantial loss of therapeutic activity by mixing the protein composition with a pasteurization-stabilizing amount of a sugar or reduced sugar and of an amino acid prior to pasteurization. Pasteurized compositions containing therapeutically active proteins, which have heretofore been unattainable, can be prepared by the method of the invention.
Abstract: A method for assaying blood coagulation factor XII in human blood plasma wherein plasma is treated with an activator in order to convert factor XII present in the plasma into factor XIIa, the latter is reacted with a tripeptide derivative which is split by the enzymatic action of factor XIIa and forms a colored or fluorescent split product, and the quantity of this split product is measured photometrically, spectrophotometrically or fluorescence-spectrophotometrically.