Boehringer Mannheim Gmbh

Scil Proteins Gmbh

Hoffmann-la Roche Inc.

Roche Diagnostics Gmbh

Rainer Rudolph

Ulrich Kohnert

Stephan Fischer

Adelbert Grossmann

Ulrike Fiedler

Elisabeth Schwarz

Erhard Kopetzki

Uwe Michaelis

Dorothea Ambrosius

Gerhard Winter

Ralf Mattes

Heinrich Woog

Markus Fiedler

Dorothee Ambrosius

Carola Dony

Joerg Schaeffner

Anke Rattenholl

Kay-Gunnar Stubenrauch

Helmut Lenz

Anne Stern

Michael Jarsch

Ulrich Martin

Helmut Burtscher

Arne Skerra

Gerald Boehm

Carola Reimann

Hauke Lilie

Susanne Richter

Martina Wunderlich

Rudolf Glockshuber

Johannes Buchner

Gether Schumacher

The invention relates to modified proteins of the superfamily of 'ubiquitin-like proteins', proteins that have a ubiquitin-like fold and fragments or fusion proteins thereof. As a result of said modification, the proteins have a binding affinity with respect to a predetermined binding partner that did not exist previously. The invention also relates to a method for the production and utilization of said proteins.

Artificial binding proteins based on ubiquitin

Generation of artificial binding proteins on the basis of ubiquitin proteins

The present invention describes novel beta-sheet proteins having specific binding properties and catalytic properties and also methods for preparing these proteins.

Beta-sheet proteins with specific binding properties

The invention relates to a method for producing biologically active &#x3b2;-NGF from the proform proNGF. After expressing the proform of the &#x3b2;-NGF in a prokaryotic host cell, the recombinant protein is isolated in the form of insoluble inactive aggregates (inclusion bodies). After the solubilization thereof in a strong denaturing agent and the subsequent conversion thereof into the natural conformation, which is determined by the disulfide bridges present in the natural &#x3b2;-NGF, biologically active &#x3b2;-NGF is obtained by subsequently splitting-off the prosequence.

Method for obtaining active pro-NGF and beta-NGF

Pharmaceutical preparations comprising human proNGF

Fabrication of beta-pleated sheet proteins with specific binding properties

A process for the production of a naturally folded eukaryotic polypeptide containing two or several cysteines linked by disulfide bridges by a) culturing prokaryotic cells in which the said prokaryotic cells contain an expression vector which codes for the said polypeptide which contains a prokaryotic signal sequence at the N-terminus, b) secreting the polypeptide into the periplasm or the medium, c) cleaving the signal sequence and isolating the polypeptide from the periplasm or the medium, which is characterized in that a nucleic acid coding for a molecular chaperone is additionally expressed in the said prokaryotic cell and the chaperone is secreted into the periplasm, is suitable for the recombinant production of polypeptides in prokaryotes in a high yield.

Process for the production of naturally folded and secreted proteins by co-secretion of molecular chaperones

A chimeric polypeptide has a first and a second polypeptide chain chemically linked via 1 to 3 cysteine-based disulfide bridges. The first polypeptide chain consists of 1 to 3 cysteines and 4 to 12 basic amino acids preferably selected from the group consisting of arginine, lysine and ornithine. The second polypeptide chain consists of 1 to 3 cysteines and 4 to 12 acidic amino acids selected from the group consisting of glutamate and aspartate. Each polypeptide chain is linked at its C- or N-terminus to a biologically active compound, and is useful as a multimeric pharmaceutical agent. A method for producing such chimeric polypeptide involves contacting the first polypeptide chain with the second polypeptide chain under conditions such that the basic amino acids on the first polypeptide chain ionically interact with the acidic amino acids on the second polypeptide chain and then treating the first polypeptide chain and the second polypeptide chain with an oxidizing agent under conditions such that the 1 to 3 cysteines of the first polypeptide chain form disulfide bridges with the 1 to 3 cysteines of the second polypeptide chain thereby forming the chimeric polypeptide.

Method for producing chimeric polypeptides

The invention concerns a process for increasing the formation of the natural protein conformation when disulfide-bonded proteins are secreted by a prokaryotic host organism that contains a recombinant DNA coding for the secreted protein whereby the host organism is cultured in a suitable culture medium under suitable conditions for the expression of the recombinant DNA, which is characterized in that a culture medium containing 0.1 to 20 mmol/l of one or several thiol reagents is used.

Yield when disulfide-bonded proteins are secreted

A process produces a water-soluble, naturally folded eukaryotic polypeptide containing two or several cysteines linked by disulfide bridges. This process involves culturing prokaryotic cells, a) in which the prokaryotic cells contain an expression vector which encodes the polypeptide which contains a prokaryotic signal sequence at the N-terminus, b) under conditions under which the polypeptide is secreted into the periplasm or the medium, c) cleaving the signal sequence and isolating the polypeptide from the periplasm or the medium. In this process, the culturing is carried out in the presence of arginine or a compound of the formula I R,&mdash;CO&mdash;NR,(I) in which R and R,represent hydrogen or a saturated or unsaturated branched or unbranched C,-C,alkyl chain and R,represents hydrogen, NHR,or a saturated or unsaturated branched or unbranched C,-C,alkyl chain, is suitable for the recombinant production of polypeptides in prokaryotes in a high yield.

Process for the production of naturally folded and secreted proteins

The present invention concerns a process for the isolation of recombinant IgA protease from inclusion bodies. In addition a recombinant DNA is claimed which codes for an IgA protease whose C-terminal helper sequence and preferably also its N-terminal signal sequence is no longer active.

Methods for making neisseria or hemophilus IgA protease and DNA encoding

Aqueous pharmaceutical preparations of G-CSF are disclosed that are stable on storage and a buffer selected from the group consisting of a salt of citrate, maleate, a combination of phosphate and citrate, and arginine; and at least one surfactant.

Aqueous pharmaceutical preparations of G-CSF with a long shelf life

Stable lyophilized pharmaceutical preparations of G-CSF

The present invention concerns a process for the isolation of recombinant core streptavidin in which host cells are transformed with a DNA coding for core streptavidin, the transformed host cells are cultured under suitable conditions, the DNA coding for core streptavidin is expressed and the recombinant core streptavidin is isolated from the host cells or the culture medium, wherein a DNA coding for core streptavidin is used which has

Recombinant core streptavidin

Process for the reactivation of denatured protein

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Weilheim, Germany

Rainer Rudolph