Takeda Chemical Industries, Inc.

Kazuaki Kitano

Ryuichi Tozawa

Shigeru Fujimoto

Yasuo Sugiyama

Hidefumi Yukimasa

Masakuni Kori

Yoshio Nakao

Takashi Sohda

Hitoshi Ikeda

Tsuneo Oda

Mitsuko Asai

Isuke Imada

Setsuo Harada

Hiroshi Morimoto

Susumu Shinagawa

Hidekazu Sawada

Kiyoshi Nara

Akira Imada

Kazuhiko Kintaka

Kazuyoshi Katamoto

Masato Kuriyama

Kazutaka Maejima

Shigeru Morita

Keiji Iwamoto

Shigeru Suzuki

N-containing, condensed heterocyclic compounds and salts thereof are disclosed which are useful for inhibiting squalene synthetase and fungal growth, and which are useful for treating or preventing hyperlipidemia. Also disclosed is a method for producing these compounds.

N-containing condensed heterocyclic compounds, their production, and

4,1-benzoxazepin derivatives and their use

There is provided a squalene inhibitory composition containing a 1,1-bisphosphonic acid compound, a lower alkyl ester thereof, or a salt thereof, which is useful for treating hypercholesterolemia. There are also provided novel compounds having squalene synthetase inhibitory activity and a pharmaceutical composition for treating hypercholesterolemia containing a 1,1-bisphosphonic compound, a lower alkyl ester thereof or a salt thereof.

Method of inhibiting squalene synthetase

There are disclosed cloning of an alkaliprotease secretion gene of a mold and a DNA fragment containing a part or all of the alkaliprotease gene. A plasmid into which the DNA fragment is integrated, a transformant obtained by using the plasmid and the production of a useful protein by using the transformant are also disclosed.

DNA coding for alkaline protease

Disclosed are (1) a hybridoma carrying a vector for expressing a fibroblast growth factor (FGF) protein gene; (2) a method for producing the hybridoma of (1) which comprises transforming a hybridoma with the vector for expressing the FGF protein gene; and (3) a method for producing a biologically active substance which comprises cultivating in a culture medium the hybridoma obtained by the method of (2) using a hybridoma producing a biologically active substance other than the FGF protein, producing the FGF protein and producing and accumulating the biologically active substance in a culture, and recovering the biologically active substance, whereby the biologically active substance can be efficiently produced and recovered using the serum-free medium, which is advantageous for industrial production and very useful for an improvement in the breeding of the hybridoma.

Fibroblast growth factor gene transformed hybridoma and enhanced

The present invention provides an improvement in a method for producing physiologically active proteins by cultivating Escherichia coli having an expression vector which contains a structural gene for such proteins at the downstream end of the translational starting codon. The method comprises cultivating the Escherichia coli in a medium containing (1) an iron ion source, a manganese ion source or a mixture thereof and (2) a nitrogen source derived from natural origin. The advantage of this method is an increase in the yield of physiologically active proteins substantially free of methionine (corresponding to translational starting codon ATG) at the N-terminus.

Method of producing interleukin-2

The present invention provides an improvement in a method for producing interleukin-2 by cultivating a transformant of Escherichia coli capable of producing interleukin-2 into a medium, which comprises inoculating said Escherichia coli into the medium of pH from about 4.8 to 6.0 and growing it while maintaining this pH range. By the method of the present invention, the interleukin-2 productivity is considerably improved.

Production of interleukin-2

A method for producing high yields of interferons which comprises cultivating a microorganism carrying an expression vector with a structural gene of interferon inserted therein in a chemically defined medium containing L-glutamic acid and an iron ion source and preferably further containing an zinc ion source or zinc and copper ion sources, and recovering interferon from the culture.

Method for producing interferons

Novel antibiotic C-19393 E.sub.5, which is produced by cultivating a microorganism belonging to the genus Streptomyces, has strong antimicrobial activity against gram-positive and gram-negative bacteria and, thus, are useful as a bactericide or disinfectant.

Pharmaceutically acceptable salts of the antibiotic C-19393 E.sub.5

A novel Antibiotic G-6302 is produced by cultivating a microorganism belonging to the genus Pseudomonas and being capable of producing Antibiotic G-6302 in a culture medium to have Antibiotic G-6302 elaborated and accumulated in the cultured broth and recovering the antibiotic. Antibiotic G-6302 is useful as a germicide or disinfectant.

Antibiotic G-6302

Ubiquinone-10 is produced by culturing a microorganism belonging to the genus Sporidiobolus or Oosporidium and capable of producing ubiquinone-10, causing the microorganism to accumulate ubiquinone-10 and recovering ubiquinone-10.

Method for producing ubiquinone-10

Deacetoxycephalosporin C can be produced with advantage by fermentation of a microorganism which belongs to the genus Streptomyces, Cephalosporium, Emericellopsis, Paecilomyces, Anixiopsis, Arachnomyces or Spriroidium and is capable of producing deacetoxycephalosporin C. Deacetoxycephalosporin C is a useful antibiotic as such or can be used as a starting material for the production of other various cephalosporin antibiotics.

Growing community of inventors

Sakai, Japan

Kazuaki Kitano