Abstract: The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modifications render Factor VIIa substantially unable to activate plasma Factors X or IX. The invention relates to novel methods of treatment and uses of modified Factor VII for preventing or treating myocardial injury associated with post-ischemic reperfusion, for improving regional myocardial blood flow during reperfusion, and maintaining or improving vascular patency in a patient, as well as topical application of modified Factor VII at vascular sites susceptible to thrombus formation.

Abstract: The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modifications render Factor VIIa substantially unable to activate plasma Factors X or IX. The invention relates to novel methods of treatment and uses of modified Factor VII for preventing or treating myocardial injury associated with post-ischemic reperfusion, for improving regional myocardial blood flow during reperfusion, and maintaining or improving vascular patency in a patient, as well as topical application of modified Factor VII at vascular sites susceptible to thrombus formation.

Abstract: The present invention relates to the use of compounds of formula I ##STR1## wherein R.sup.1 is independently hydrogen, hydroxy, alkyl with 1 to 6 carbon atoms, acyloxy groups with 1 to 6 carbon atoms, alkyloxy with 1 to 6 carbon atoms or from 1 to 5 sugar moieties; and R.sup.2 is independently hydrogen, or alkyl with 1 to 6 carbon atoms, in the reduction of coagulation time in mammals.

Abstract: A coagulation active complex of Factor VIII fragments is produced by causing coagulation inactive FVIII heavy chain to react with coagulation inactive FVIII light chain in the presence of a complex forming agent. Thus, FVIII-HC and FVIII-LC are converted to coagulation active FVIII complex in the presence of divalent metal ions, such as Mn.sup.2+, Ca.sup.2+ or C.sup.2+, or a component of the pro-thrombin complex.

Abstract: A coagulation active complex of Factor VIII fragments is produced by causing a coagulation inactive FVIII heavy chain to react with a coagulation inactive FVIII light chain in the presence of a complex forming agent. Thus, FVIII-HC and FVIII-LC are converted to coagulation active FVIII complex in the presence of metal ions, such as Mn.sup.2+, Ca.sup.2+, or Co.sup.2+ or a component of the prothrombin complex or a substance having reactivity to compounds containing the group --SH and/or --S--S.

Abstract: Methods and compositions are provided for recombinant DNA production of Factor VIIIC and truncated derivatives thereof. Based on amino acid sequences, probes are developed for isolating messenger RNA, cDNA and/or chromosomal DNA encoding for Factor VIIIC. The Factor VIIIC gene in its entirety, a fragment thereof, or a cDNA is then used for expression of Factor VIIIC in a host.The bacteriophage .lambda.FVIII23D containing the 14.43kb EcoRI fragment was deposited at the A.T.C.C. on Jan. 4, 1984 and given Accession No. 40094. Also, the vector pSVF8-200 was deposited at the A.T.C.C. on July 17, 1985 and given Accession No. 40190.

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: Hybridomas producing monoclonal antibodies specific for polypeptide fragments derived from human Factor VIIIC are provided. Class I hybridomas produce monoclonal antibodies reactive with a 80/77 kd doublet fragment or with both the 80/77 kd doublet and a 240 kd polypeptide. Class III hybridomas produce monoclonal antibodies reactive with the 240 kd polypeptide as well as a 92.5 kd fragment and its precursors. Class III antibodies show additional reactivity with a 40 kd thrombin digestion product. The monoclonal antibodies are useful for the separation of Factor VIIIC and its constituent polypeptides, as well as for the immunoassay of Factor VIIIC in biological samples.

Abstract: Production of a high purity concentrate of the antihemophilic Factor VIII (AHF) by precipitation of an aqueous solution of cryoprecipitate from blood plasma in a first step with such an amount of polyethylene glycol (PEG), preferably about 4% by weight, as will precipitate a substantial amount of the present fibrinogen, subjecting the fibrinogen-free solution to a second precipitation step with preferably about 12% by weight of PEG in the presence of a salting-in agent, such as an amino acid, in particular lysine or arginine, or a carbohydrate, and then recovering the precipitate with a concentrated content of the present Factor VIII. The obtained Factor VIII concentrate with a very low content of immunoglobulins and other plasma proteins has a solubility in an aqueous injection medium of 45 to 500 units/ml and a high specific activity of up to 50 units/mg protein.

Abstract: An antihemophilic factor preparation (AHF) of high solubility and long half-life is produced in high yields by complete or partial thawing of deep-frozen human blood plasma by irradiation with electromagnetic waves of a frequency of about 10.sup.8 -10.sup.15 for a period of time and with an energy penetration such that the temperature in the thawed plasma does not exceed 10.degree. C. at any point, and processing in a manner known per se by centrifuging the thawed product to form a cryoprecipitate, redissolving the cryoprecipitate in a buffer and isolating a concentrated solution which, if desired, is freeze-dried. Irradiation is preferably effected by microwaves of a frequency of 10.sup.8 -3.times.10.sup.11 Hz, in particular 2.times.10.sup.9 -3.times.10.sup.10 Hz, or by infrared light, said frozen plasma being preheated if desired.The preparation is suitable for injection performed by the patient himself without medical assistance.