Zymogenetics, Inc.

Eisai Company, Limited

Shinji Yoshitake

Eileen R Mulvihill

Suguru Suzuki

Akira Hashimoto

Teruaki Yuzuriha

Bjorn A Nexo

Yasunori Ikeda

Donald C Foster

Patrick J O'Hara

Yoshiharu Mizui

Naoko Nagaoka

Toshio Seto

Hiroyuki Kato

Kurt Pingel

Noboru Suzuki

Tissue plasminogen activator analogs containing the growth factor domain of native t-PA, the domain having at least one cysteine residue replaced with another amino acid. The t-PA analogs may further contain a variety of substitutions and/or modifications. Pharmaceutical compositions containing one or more of the t-PA analogs along With a physiologically acceptable carrier or diluent are also disclosed.

Tissue plasminogen activator analogs having modified growth factor

A novel human antithrombin III (AT III) mutant having a high antithrombin activity in the absence of heparin and effective in the treatment of thrombotic disorders as an anticoagulant, which is obtained by mutating amino acids at the reactive site and the heparin binding site of human AT III into another amino acids with the use of the recombinant DNA technology with the use of a DNA coding for AT III as a template. The invention also relates to a method for mass producing the above-described mutant by incubating a host transformed by an expression vector having the cDNA of the mutant inserted therein.

Human antithrombin III mutants

Zymogens of proteins having fibrinolytic activity are disclosed. The proteins are cleavable by thrombin, the cleavage resulting in the stimulation of fibrinolytic activity. Suitable proteins which may be modified in accordance with the present invention include tissue plasminogen activator, urokinase, and plasminogen variants. The modified molecules are substantially clot-specific, in view of the large amounts of thrombin associated with clots in vivo.

Thrombin-activated tissue plasminogen activators

Tissue plasminogen activator analogs exhibiting greater specificity for fibrin than native t-PA are disclosed. The analogs include the K1 domain of native t-PA replaced with another kringle domain mediating the binding of the analog to fibrin. The kringle contains six cysteine residues. The t-PA analogs may further include a variety of substitutions and modifications. Pharmaceutical compositions containing one or more of the t-PA analogs along with a physiologically acceptable carrier or diluent are also disclosed.

Modified t-PA with kringle-/replaced by another kringle

Growing community of inventors

Ibaraki, Japan

Shinji Yoshitake