Japan Energy Corporation

Nippon Mining Co., Ltd.

Fuji Yakuhin Kogyo Kabushiki Kaisha

Satoru Misawa

Akiko Sukesada

Hitoshi Matsuda

Tadanori Morikawa

Kyoichi Kobashi

Hideyuki Furuya

Masaharu Nakano

Ryo Muramatsu

Yoshifumi Inoue

Eriko Nukui

Koichi Wada

Disclosed are hirudin analogs, a method of manufacture thereof, and anticoagulant compositions containing the same. Sequences Asp.sup.33 -Gly.sup.34 or Asp.sup.62 -Ala.sup.63 of naturally-occurring hirudins or their analogs were substituted as disclosed to suppress the formation of succinimide- or beta- forms, thereby yielding hirudin analogs with high stability, high anti-thrombin activity, and therapeutic potential as anticoagulants. Hirudin analogs having Val.sup.1 -Val.sup.2 of naturally-occurring hirudin substituted with Ile.sup.1 -Ile.sup.2 are preferred for their high antithrombiin activity. The invention also provides DNAs encoding the amino acid sequence of hirudin analogs, expression vectors, recombinant microogranisms, and a method of manufacturing hirudin analogs using recombinant microorganisms.

Hirudin analogs, methods of manufacture thereof and anticoagulant

The present invention relates to hirudin variants having high anti-thrombin and anti-platelet activity, methods for producing them, and anti-coagulants having said variants as active ingredients. Hirudin variants shown in formula (I) having tyrosine residues or having their hydroxyl group sulfated. Methods for producing hirudin variants by sulfating hydroxyl group of said tyrosine residues, and anti-coagulants having hirudin variants shown in formula (I) as active ingredients.

Anticoagulant hirudin variants and methods for their production

Provided is a chimeric HV1/HV3 hirudin analog useful as an anti-coagulant, exhibiting higher anti-thrombin activity and less tendency to cause bleeding than hirudin HV1. Also provided are a method of producing hirudins and hirudin analogs, as well as other proteins, employing secretion vectors, and transformed microorganisms such as E. coli. Pharmaceutical compositions comprising various hirudins or the chimeric HV1/HV3 hirudin analog of the present invention and a pharmaceutically acceptable carrier are also disclosed.

Secretion vector for hirudin or hirudin analog production

Production of a new hirudin analog and anticoagulant pharmaceutical

Growing community of inventors

Toda, Japan

Satoru Misawa