Ciba-geigy Corporation

Novartis Corporation

Novartis Ag

Behringwerke Aktiengesellschaft

Ucp Gen-pharma Ag

Movartis Ag

Ciba-geigy Corporation a Corp. of New York

Bernd Meyhack

Jutta Heim

Hans Rink

Markus G Grutter

Albert Schmitz

Nico Cerletti

Manfred Liersch

Bhabatosh Chaudhuri

Sefik Alkan

Walter Marki

Jan Van Oostrum

David Cox

Fredericus A Asselbergs

Gary Kent McMaster

Bhanu Rajput

Jacob B Visser

Christof Gysler

Michael Broker

Michael Br&ouml;ker

Albert Hinnen

Hermanus C Kester

Walter M&auml;rki

Rolf Burgi

A method for the production and secretion of proteins with hirudin activity in an eukaryotic host organism is provided. There are also provided hybrid vectors comprising a DNA sequence encoding a signal peptide upstream of and in reading frame with the structural gene for desulphatohirudin, and eukaryotic host organisms transformed with said hybrid vectors.

Production of thrombin inhibitors

The invention pertains to the field of recombinant DNA technology and concerns a method for the production of a protein heterologous to yeast in a homogenous form with the aid of,strain HT393 or a derivative thereof carrying a hybrid vector containing the genes for said protein.

Process for the production of proteins

The invention relates to a process for the production of biologically active, dimeric TGF-.beta., to novel TGF-.beta.s and pharmaceutical compositions comprising it. TGF-.beta. produced by this process can be used in various therapeutic modalities.

Process for refolding recombinantly produced TGF-.beta.-like proteins

The invention relates to DNA sequences that code for the amino acid sequence of the thrombin inhibitor hirudin, hybrid vectors containing such DNA sequences, host cells transformed with such hybrid vectors, novel polypeptides with thrombin-inhibiting activity produced from such transformed host cells, processes for the manufacture of these DNA sequences, hybrid vectors and transformed host cells, and processes for the manufacture of these thrombin-inhibitors using the transformed host cells. The hirudin compounds that can be produced according to the invention have valuable pharmacological properties.

Process for the manufacture of thrombin inhibitors

The process for the production of a dimeric, biologically active Transforming Growth Factor type .beta. (TGF-.beta.)-like protein or a salt thereof, comprising refolding the denatured monomeric form of the protein in the presence of a mild detergent that permits folding of the monomeric protein into a spatial conformation, which after dimerization, is the conformation associated with the biological activity, while retaining the monomeric protein in soluble form. Mild detergents include sulfobetaines, 3-(3-chlolamidopropyl)dimethylammonio-1-propanesulfonate, 3-(3-chlolamidopropyl)dimethylammonio-2-hydroxy-1-propane-sulfonate, digitonin, cholate and deoxycholate at a concentration of about 1 to 100 mM. Compositions containing a TGF-.beta.-like protein produced according the invention can be used for the promotion and acceleration of wound healing and bone and tissue repair, cancer treatment, bone marrow protective agent, as a mediator of cardio-protection, as an anti-inflammatory or immunosuppressive agent, or as a growth regulator in mammalian cell cultures.

Novel single-chain hybrid plasminogen activators having an amino acid sequence composed of at least two subsequences corresponding in amino acid identity and number to subsequences of human t-PA and of human u-PA, and mutants thereof in which at least one of the N-glycosylation sites is modified such that glycosylation cannot take place at these sites exhibit valuable pharmacological properties. The hybrid plasminogen activators are produced by recombinant DNA technology.

Hybrid plasminogen activator

Recombinant DNA molecules coding for pectin lyase (PL) expression systems and derivatives thereof, such as the structural genes of PLA, PLB, PLC, PLD, PLE and PLF, and corresponding regulatory sequences, e.g. promoter, signal and terminator sequences, and hybrid vectors comprising corresponding DNAs, including hybrid vectors with DNA coding for homologous or heterologous polypeptides, hosts, especially filamentous fungi, e.g. Aspergillus hosts, transformed by said vectors, methods for the preparation of said recombinant DNA molecules and said hosts and the use of the recombinant DNA molecules for the preparation of new expression systems. A further objective is the preparation of polypeptides by means of said DNAs and said hosts.

Pectin lyase genes of aspergillus niger

Novel upstream activation sites of the yeast PHO5 gene are used to produce inducible yeast hybrid promoters. The yeast hybrid promoters can be used to control transcription of a polypeptide coding region foreign to yeast in a yeast expression vector.

Repressible yeast promoters

DNA molecules encoding hybrid proteins of tissue plasminogen activator

Novel human plasminogen activators of the urokinase type are produced by yeast cells transformed with a hybrid vector comprising a DNA sequence coding for said human plasminogen activator. Novel hybrid vectors, yeast hosts transformed with such hybrid vectors and processes for the production thereof are also provided. 77

Process for the production of urokinase using Saccharomyes cerevisiae

Growing community of inventors

Magden, Switzerland

Bernd Meyhack