Zymogenetics, Inc.

Eisai Company, Limited

Akira Hashimoto

Eileen R Mulvihill

Suguru Suzuki

Shinji Yoshitake

Yasunori Ikeda

Bjorn A Nexo

Teruaki Yuzuriha

Yoshikazu Hasegawa

Masayuki Konishi

Tsunehiko Kataoka

Koichi Ogawa

Yoshiaki Nagara

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

Culture medium is circulated from a culture medium tank, through a first main duct, through a cell cultivating vessel containing therein a bundle of hollow threads, through a second main duct and back to the culture mediun tank. The first main duct is provided at an intermediate point with a vibrating columnar pump adapted to pulsate the culture medium and to vibrate outer surfaces of said hollow threads. The second main duct is provided along a tail end portion with a container serving to capture solids in the culture medium. The first main duct branches into a first sub-duct which is provided with sensors used to detect and regulate a quantity of gas mixture in the culture medium. Similarly, the second main duct branches into a second sub-duct which is provided with sensors used to detect a quantity of gas mixture in the culture medium which has been used for cell cultivation so that a level of cell metabolism occurring in the hollow threads may be detected and a flow velocity of the culture medium may be correspondingly regulated.

Cell cultivating apparatus

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

A process is disclosed for purifying elastase by precipitating elastase from an aqueous, elastase-containing solution, in which the electroconductivity of said aqueous solution is adjusted to 3 millimhos per centimeter or less and the pH of the solution is adjusted to a value of from 2 to 5. The electroconductivity of said aqueous solution is preferably adjusted to 3 millimhos per centimeter or less by means of ultrafiltration.

Process for purifying elastase

Growing community of inventors

Ryugasaki, Japan

Akira Hashimoto