Abstract: Cells which constitutively express IGF-1 and IGF-1 R cDNAs are provided. These cells are useful for the production of selected proteins. Methods for producing the cells are also provided. Diagnostic and therapeutic methods are provided using cells transfected with IGF-1 R.

Abstract: Tissue plasminogen activator (t-PA) zymogens and variants are prepared, including a fibrinolytically active variant of t-PA that has an amino acid alteration at a site within the protease domain of t-PA as compared with the corresponding wild-type t-PA, which alteration renders the variant zymogenic in the presence of plasmin-degraded fibrinogen, and/or fibrin (or plasma clot) specific, as compared to the corresponding wild-type t-PA. DNA sequences can be prepared that encode the zymogens and variants, as well as expression vectors incorporating the DNA sequences, and host cells transformed with the expression vectors. The zymogens and variants may be used in a pharmaceutical preparation to treat a vascular disease or condition or to prevent fibrin deposition or adhesion formation or reformation in mammals.

Abstract: Thrombolytic proteins are disclosed which have tissue plasminogen-type activity. The proteins are characterized by modification within the 94 amino acid N-terminus, and/or at Arg-275, and/or at one or more of the N-linked glycosylation sites. Methods for making these proteins are disclosed as are therapeutic compositions containing same.

Abstract: DNA isolates coding for insulin-like growth factor binding protein may be used to produce the protein via recombinant expression systems. Insulin-like growth factor binding protein, which generally has a molecular weight of about 53 kD on non-reducing SDS-PAGE, is useful as a binder to insulin-like growth factor and as a metabolic regulator.

Abstract: A tissue plasminogen activator (t-PA) variant is prepared that has an amino acid deletion at positions 466 to 470 of the corresponding wild-type t-PA. This alteration renders the variant fibrin (and plasma clot) specific as compared to the corresponding wild-type t-PA. DNA sequences can be prepared that encode the variant, as well as expression vectors incorporating the DNA sequences, and host cells transformed with the expression vectors. The variant may be used in a pharmaceutical preparation to treat a vascular disease or condition or to prevent fibrin deposition or adhesion formation or reformation in mammals.

Abstract: Biologically active tissue plasminogen activator (t-PA) variants with decreased clearance as compared to wild-type t-PA are prepared, including variants that have one or more amino acid alterations in at least the kringle-1 and/or kringle-2 domain(s) of the molecule. DNA sequences can be prepared that encode the variants, as well as expression vectors incorporating the DNA sequences and host cells transformed with the expression vectors. The variants may be used in pharmaceutical preparations to treat a vascular disease or condition, or to prevent fibrin deposition or adhesion formation or reformation in mammals.

Abstract: A modified t-PA having improved in vivo half-life is disclosed comprising in sequence a fibronectin finger-like domain F, a growth factor domain GF, a sequence of two K2 kringle regions and a serine protease region SP, wherein the first of said kringles is free of any glycosylation site and the second of said kringles has a single glycosylation site.

Abstract: The invention discloses modified forms of the enzyme tissue plasminogen activator (t-PA) in which recombinant DNA techniques are utilized to modify the structure of the t-PA cDNA to express a modified t-PA which retains the ability to activate plasminogen yet binds less efficiently to plasmin inhibitor. The invention provides novel DNA compounds and recombinant DNA expression vectors that encode modified human t-PA wherein all or a portion of the kringle protein domains of native human t-PA are removed. Both eukaryotic and prokaryotic expression vectors containing the modified t-PA DNA have been constructed and used to transform Chinese hamster ovary cells and Escherichia coli cells.

Abstract: An analog of porcine growth hormone, is disclosed which retains the diabetogenic, insulin-sparing and lipolytic properties of porcine growth hormone while being capable of improving growth in mammals.

Abstract: A cDNA having a base sequence for human vascular permeability factor has been cloned and characterized and the amino acid sequence of the human vascular permeability factor protein has been determined.

Abstract: A purified fibrinolytically active degraded species of tissue-type plasminogen activator comprising a fibrinolytically intact B chain of native t-PA linked to kringle 2 as the only functionally and structurally intact domain of native t-PA A chain.

Abstract: Tissue plasminogen activator (t-PA) analogues have at least one substitution in the growth factor (GF) domain that at least partially reduces hepatic receptor binding without substantially jeopardising physico-chemical stability in blood or fibrinolytic activity. This results in a longer plasma half life. Substitutions in the beta-sheet encompassing residues 63-72, especially at Leu 66 and/or Tyr 67 and/or Phe 68, are particularly preferred.

Abstract: Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45 kDa endothelial cell mitogen that has been purified to homogeneity from human platelets. It does not bind to heparin and does not stimulate the proliferation of fibroblasts, in contrast to other endothelial mitogens of the fibroblast growth factor (FGF) family. PD-ECGF appears to be the only endothelial cell growth factor in human platelets and recent data indicate that it has angiogenic activity in vitro, i.e., the ability to stimulate the formation of new blood vessels and chemotactic activity, in vitro. The present invention provides a homogeneous PD-ECGF in substantially greater yields than available in the past, the primary structure of PD-ECGF, antibodies against PD-ECGF, clones of its cDNA, and variants thereof. The invention also provides a therapeutic preparation of PD-ECGF.

Abstract: A new thrombolytically active protein is not glycosylated and consists of the following amino acid sequence: ##STR1## or said amino acid sequence with an additional N-terminal methionine. DNA sequences encoding the thrombolytically active, non-glycosylated protein and pharmaceutical compositions containing said protein are also disclosed. The protein possesses particularly favorable properties when used to dissolve blood clots.

Abstract: DNA encoding two forms of PDGF A-chain polypeptide, the construction of expression vectors for expressing such DNA in yeast and mammalian cells, and the expression of such DNA in yeast and mammalian cells to produce active PDGF A-chain homodimer and active PDGF A-chain/B-chain heterodimer are disclosed.

Abstract: Isolated DNA sequences, expression vectors and transformant cells are provided which allow for the large scale production of vascular endothelial cell growth factor. The vascular endothelial cell growth factor is useful in the treatment of wounds in which neovascularization or reendothelialization is required for healing.

Abstract: A process for the preparation of a recombinant IGF-II (rIGF-II) without a covalently attached foreign protein moiety and without N-terminal attached methionine or a derivative of methionine or of a salt of said IGF-II, rIGF-II produced by said method, hybrid vectors comprising DNA encoding said rIGF-II, hosts transformed with said vectors, and a process for the isolation of said rIGF-II from the host cell and refolding it into a biologically active form.

Abstract: The present invention relates to novel fragments of basic fibroblast growth factor (bFGF). The mitogenic potency of one of these bFGF fragments, identified as HBF-2 is about 25-50 fold less than that of native bFGF but at least 10.sup.3 -10.sup.4 fold more active than that of previously reported synthetic fragments of bFGF. Therefore, the present invention provides the shortest fragment of bFGF that retains substantial biologic activity.

Abstract: High molecular weight forms of therapeutic proteins are disclosed which are single-polypeptide-chain proteins that contain the same or similar therapeutic activity as the therapeutic protein. In particular, high molecular weight forms of the human bFGF angiogenic factor are disclosed which are single-polypeptide-chain proteins having at least one active site possessing an activity selected from the group consisting of mitogenic activity, chemotactic activity, angiogenic activity, neurotrophic, activity, the ability to stimulate protease synthesis and combinations thereof. The high molecular weight angiogenic factors exhibit substantial homology to and are immunologically equivalent to the native high molecular weight forms isolatable from human hepatoma cells. The high molecular weight angiogenic factors are produced by DNA translation initiating at non-ATG codons and incorporate additional polypeptide sequences N-terminal to the human bFGF factor.

Abstract: Compositions and methods of the synthesis of hybrid streptokinase with fibrin binding domains based on gene fusion technology. Recombinant DNA methods have been used to fuse gene segments for streptokinase and for fibrin-binding domains and express the fused gene in prokaryotic microorganisms, and the respective expressed protein is subsequently obtained by biotechnologic fermentation for the purpose of use in clinical medicine.