Human tissue plasminogen activator

Fig. 7. The arrangement of domains along human tissue plasminogen activator (SWISS-PROT UROT HUMAN, top of the figure) and human Factor XII (SWISS-PROT FA12 HUMAN, bottom of the figure). FNI and FNII are fibronectin class I and II domains, respectively.

Van Reis et al. [92] reported the scale-up of a HF system for the recovery of human tissue plasminogen activator (t-PA) produced by recombinant CHO cells from the 2.5-m to the 180-m scale. A robust and reproducible process was achieved by combining hnear scale-up principles, control of fluid dynamic parameters and experimentally defined limits of product retention, which meant maintaining channel length, wall shear rate and flux constant. 

Activase (Alteplase) [CHO-expressed glycoprotein-recombinant human tissue plasminogen activator] Genentech Lyophilized (50 mg single-dose vial 100 mg single dose vial) 50 and 100 mg doses to be reconstituted with 50 or lOOmL of WFI, respectively Per 50 mg vial 1.7 g L-arginine 0.5 g phosphoric acid < 4 mg polysorbate 80 (under vacuum) Per 100 mg vial 3.5 g L-arginine 1 g phosphoric acid <11 mg polysorbate 80 (without vacuum) IV... 

Reteplase (Retavase) and tenecteplase (TNKase) are newer thrombolytics. These agents are derived of human tissue plasminogen activator, and therefore... 

Haggroth L, Mattsson C, Friberg J. Inhibition of the human tissue plasminogen activator in plasma from different species. Thromb Res 1984 33 583-94. 

Fuchs HE, Berger HB, Pizzo SV. Catabolism of human tissue plasminogen activator in mice. Blood 1985 65 539 14. 

Matsuo O, Rijken DC, Collen D (1981) Thrombolysis by human tissue plasminogen activator and urokinase in rabbits with experimental pulmonary embolus. Nature 291 590-591 Nicolini FA, Lee P, Rios G et al. (1994) Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis. Circulation 89 1802-1809... 

Zhang L, Zhang ZG, Liu X, Hozeska A, StagUano N (2006) Treatment of embolic stroke in rats with bortezomib and recombinant human tissue plasminogen activator. Thromb Haemost 95 166-173... 

Lau, D., Kuzma, G., Wei, C-M., Livingston, D.J., and Hsiung, N. (1987). A modified human tissue plasminogen activator with extended half-life in vivo. Bio/Technology 5,953 958. 

During detailed characterization of a tryptic map of recombinant human tissue plasminogen activator (rtPA), a minor peak was resolved whose mass was not consistent with the expected set of tryptic peptides (L. Keyt and S.-L. Wu, unpublished observation). N-terminal sequence analysis of this fraction showed that it had a sequence containing residues 276-296 of rtPA with Lys-277 present as Hyl. We developed a modified amino acid analysis program capable of detecting hydroxylysine at levels down to 0.05 residues/mol to determine the distribution of Hyl in rtPA as well as in some other proteins derived from mammalian cells. 

Zhang L, Zhang ZG, Zhang RL, Lu M, Krams M, Chopp M (2003) Effects of a selective CDl lb/ CD 18 antagonist and recombinant human tissue plasminogen activator treatment alone and in combination in a rat embolic model of stroke. Stroke 34 1790-1795... 

USA alteplase antithrombotic Activase Actilyse, Activacin, Cathflo Activase, GRTPA Recombinant human tissue plasminogen activator, glycoform alpha produced in CHO cells Thrombosis... 

Berg DT, Burck PJ, Berg DH, Grinnell BW. 1993. Kringle glycosylation in a modified human tissue plasminogen activator improves functional properties. Blood 81, 1312-1322. 

The first successful therapeutic protein made in a transgenic system was human tissue plasminogen activator regulated by a milk-directed promoter for accumulation in mouse milk [5]. Human growth hormone, which was one of the first proteins produced using recombinant microbial systems in the early 1980s, became the first human protein expressed in plants (tobacco cells) in 1986 [6]. Since then, over 200 biotherapeutics of diverse origin. 

Ebert KM, Ditullio P, Barry CA, et al. Induction of human tissue plasminogen activator in the mammary gland of transgenic goats. Biotechnology (NY), 1994 12(7) 699-702. 

Human platelet-derived growth factor, see PDGF Human protein processing 774 Human retinal pigment epithelial (hRPE) 325 Human serum albumin (HSA) 275 Human somatic cell nuclear transfer 273 Human tissue plasminogen activator... 

Hoylaerts, M., et al., Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem, 1982. 257(6) p. 2912-9. 

Human tissue plasminogen activator, purified, glycosylated, 527 aa purified from CHO cells. 

Human tissue plasminogen activator, purified, glycosylated, 527 residues purified from CHO cells. Eminase is a lyophilized formulation of anistreplase, the p-anisoyl derivative of the primary Lys-plasminogen-streptokinase activator complex (a complex of Lys-plasminogen and streptokinase). A p-anisoyl group is chemically conjugated to a complex of bacterial-derived streptokinase and human plasma-derived Lys-plasminogen proteins. 

Figure 8.3. Modular structure of two proteins involved in blood clotting. Schematic representation of the modular structure of human tissue plasminogen activator and coagulation factor XII. A module labeled C is shared by several proteins involved in blood clotting. FI and F2 are frequently repeated units that were first seen in fibronectin. E is a module resembling epidermal growth factor. A module known as a "kringle domain" is denoted K.

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