Abstract: Tissue plasminogen activator (t-PA) derivatives are produced in useful quantities using recombinant DNA techniques. Specific derivatives include amino acid deletion derivatives and amino acid substitution derivatives. A deletion derivative lacking the N-terminal first 68 amino acids is specifically exemplified having requisite t-PA characteristics. The invention disclosed thus enables the production of t-PA derivatives via recombinant means. Methods, expression vehicles and various host cells useful in the production of said t-PA derivatives are also disclosed.

Abstract: Biologically active mutant tissue plasminogen activators are disclosed wherein site directed mutagenesis, for example, of a two-chain activation site renders said mutants resistant to conversion to the two-chain form. In addition, mutant tissue plasminogen activators are disclosed which have amino acid substitutions or deletions in the region of positions 274-277, which may or may not be resistant to conversion to the two-chain form, but show enhanced fibrin specificity relative to wild-type tissue plasminogen activator.

Abstract: Human tissue plasminogen 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.

Abstract: A recombinant DNA vector is provided that expresses exons of genomic DNA fragments that are inserted into the vector. The vector contains a promoter and a genomic DNA fragment so characterized and configured that the vector, upon transcription in a transfected eukaryotic cell culture, expresses the corresponding RNA segment of the genomic DNA fragment free of any intron.

Abstract: Functional human factor VIII produced recombinantly is used in the treatment of human beings diagnosed to be deficient in factor VIII coagulant activity. Also provided are DNA isolates and expression vehicles encoding functional human factor VIII, as well as transformed host cells and processes for producing human factor VIII by use of recombinant DNA technology.

Abstract: Functional human factor VIII produced recombinantly is used in the treatment of human beings diagnosed to be deficient in factor VIII coagulant activity. Also provided are DNA isolates and expression vehicles encoding functional human factor VIII, as well as transformed host cells and processes for producing human factor VIII by use of recombinant DNA technology.

Abstract: Functional human factor VIII produced recombinantly is used in the treatment of human beings diagnosed to be deficient in factor VIII coagulant activity. Also provided are DNA isolates and expression vehicles encoding functional human factor VIII, as well as transformed host cells and processes for producing human factor VIII by use of recombinant DNA technology.

Abstract: Functional human factor VIII produced recombinantly is used in the treatment of human beings diagnosed to be deficient in factor VIII coagulant activity. Also provided are DNA isolates and expression vehicles encoding functional human factor VIII, as well as transformed host cells and processes for producing human factor VIII by use of recombinant DNA technology.

Abstract: DNA enclosing a tissue factor protein mutant capable of neutralizing the ability of endogenous tissue factor to induce coagulation is provided. A representative tissue factor mutant designated K165A, K166A TF is useful in a method for inhibiting thrombin-induced platelet aggregation in a mammal, either separately or in combination with a thrombolytic agent, an anticoagulant, or a GPII.sub.blll.sub.a inhibitor.

Abstract: The present invention relates to a method and therapeutic composition for the treatment of myocardial infarction comprising administration of a tissue factor protein antagonist and a thrombolytic agent.

Abstract: Human tissue plasminogen 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.

Abstract: A method for producing tissue plasminogen activator (t-PA)in eukaroytic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild-type DHFR with methotrexate.

Abstract: A tissue factor protein mutant capable of neutralizing the ability of endogenous tissue factor to induce coagulation is provided. A representative tissue factor mutant designated K165A, K166A TF is useful in a method for inhibiting thrombin-induced platelet aggregation in a mammal, either separately or in combination with a thrombolytic agent, an anticoagulant, or a GPII.sub.b III.sub.a inhibitor.

Abstract: A method for producing tissue plasminogen activator (t-PA) in eukaryotic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild-type DHFR with methotrexate.

Abstract: Novel single-chain protease resistant urokinase derivatives are provided. In particular, derivatives are provided wherein the Lys.sub.135 Lys.sub.136 and Arg.sub.156 to Lys.sub.158 sites are rendered less susceptible to proteolytic cleavage are provided by occluding the sites or by covalently modifying them. Preferred covalent modifications are amino acid sequence variants at the sites where proteolysis of urokinase occurs. These are optimally produced by synthesis of single-chain urokinase mutants in recombinant cell culture. The novel urokinase derivatives herein offer the advantage of avoiding the generation of substantial two-chain urokinase, either in vivo or during recombinant cell culture. However, the derivatives continue function to activate plasminogen in initiating blood clot lysis.

Abstract: Human tissue plasminogen 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. A truncated human tissue plasminogen activator consisting essentially of amino acids 69-527 is produced using recombinant DNA techniques.

Abstract: Human urokinase is produced using recombinant DNA techniques. The invention disclosed thus enables the production of urokinase 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.

Abstract: Biologically active mutant tissue plasminogen activators are disclosed wherein site directed mutagenesis, for example, of a two-chain activation site renders said mutants resistant to conversion to the two-chain form.

Abstract: A method and therapeutic composition for the treatment of bleeding disorders, for example those characterized by a tendency toward hemorrhage or a hypercoagulative state, by the administration of tissue factor protein or antagonists thereof.

Abstract: A method for producing tissue plasminogen activator (t-PA) in eukaryotic host cells is disclosed. Enhanced levels of t-PA production are obtained by co-amplification of the t-PA gene through treatment of cultures transformed with mutant or wild type DHFR with methotrexate.