Merck Patent Gmbh

Merck Patent Gesellschaft MIT Beschrankter Haftung

Merck Patent Gesellschaft

Merck Gmbh

Wolfgang Strittmatter

Uwe Hofmann

Bernhard Scheuble

Siegfried Matzku

Zisi Fotev

Johannes Gleitz

Christopher Barnes

Detlef Güssow

Carlota-Silvia Jaggle

Ilka Von Hoegen

Jürgen Hemberger

Matthias Frech

Uwe Horn

Andreas Pl&uuml;ckthun

Stefan Meuer

Marian Kujau

Dieter Riesenberg

Rupert Handgretinger

Jörg Stadlmüller

J&uuml;rgen Hemberger

Detlef G&uuml;ssow

Ulrike Riesenberg

Uwe Kn&uuml;peer

Rolf Wenderoth

Anke Krebber

Heidrun Moll

Wolfgang Holzer

Burkhart Shraven

Martin Wild

Karin Schilbach-Stueckle

This invention relates to a new method for improving functional protein expression whereby the folding process is monitored by online measurement and, if required, the protein folding is influenced by adding folding promoting agents and/or co-expression of the periplasmic chaperone (Skp). In this respect, the invention offers a technology to improve the yield of functionally expressed recombinant proteins.

Method for improved protein expression in bacteria by monitoring and modulating protein folding

The present invention relates to the polypeptide Saratin and its use for the manufacture of a medicament having the capability to significantly decrease platelet adhesion and platelet accumulation after vascular injuries or endarterectomy. The invention furthermore relates to a novel medical use of Saratin as an inhibitor of thrombosis and intimal hyperplasia, where the Saratin polypeptide may be used locally as a topical agent or as a coating on, or otherwise incorporated or associated with medical devices or vascular grafts.

Specific mechanism for inhibiting platelet adhesion to collagen

A naturally occurring protein isolated from the saliva of the medicinal leechis described which strongly binds to collagen thus acting as an inhibitor of natural platelet adhesion to collagen. The protein has a molecular weight of about 12,000, an acidic isoelectric point and contains six cysteins. The protein was sequenced and the gene was cloned from acDNA-library. Procedures for producing such polypeptide by recombinant techniques are disclosed. The recombinant and the natural occurring proteins are potent inhibitors of collagen-dependent platelet adhesion and therefore useful for the therapeutic treatment of various conditions related to heart disease and diseases of the circulation system. Furthermore, the protein is useful for coating natural or artificial collagen surfaces in order to render them nonadhesive for cells and prevent the activation of cells.

Protein for blocking platelet adhesion

The present invention relates to new fusion proteins which consist of a tumor-associated targeting element preferentially a monoclonal antibody or a fragment thereof recognizing a molecule which is preferentially expressed on human tumor cells such as the human epidermal growth factor receptor (EGFR), and a biologically active ligand such as a growth and/or differentiation factor. The resulting fusion protein may be used to deliver the biologically active ligand to a specific target cell or tissue. The new immunoconjugates can be used in tumor therapy.

Immunoconjugates

A naturally occurring protein isolated from the saliva of the medicinal leechis described which strongly binds to collagen thus acting as an inhibitor of natural platelet adhesion to collagen. The protein has a molecular weight of about 12,000, an acidic isoelectric point and contains six cysteins. The protein was sequenced and the gene was cloned from acDNA-library. Procedures for producing such polypeptide by recombinant techniques are disclosed. The recombinant and the natural occurring proteins are potent inhibitors of collagen-dependent platelet adhesion and therefore useful for the therapeutic treatment of various conditions related to hard disease and diseases of the circulation system. Furthermore the protein is useful for coating natural or artificial collagen surfaces in order to render them nonadhesive for cells and prevent the activation of cells.

Use of the polypeptide Saratin for the manufacture of a medicament having the capability to significantly decrease platelet adhesion and platelet accumulation after vascular injuries or endarterectomy. The invention furthermore relates to a novel medical use of Saratin as an inhibitor of thrombosis and intimal hyperplasia, wherein the Saratin polypeptide may be used locally as a topical agent or as a coating on, or otherwise incorporated or associated with medical devices.

Saratin for inhibiting platelet adhesion to collagen

A naturally occurring protein isolated from the saliva of the medicinal leech is described which strongly binds to collagen thus acting as an inhibitor of natural platelet adhesion to collagen. The protein has a molecular weight of about 12,000, an acidic isoelectric point and contains six cysteins. The protein was sequenced and the gene was cloned from a cDNA-library. Procedures for producing such polypeptide by recombinant techniques are disclosed. The recombinant and the natural occurring proteins are potent inhibitors of collagen-dependent platelet adhesion and therefore useful for the therapeutic treatment of various conditions related to heart disease and diseases of the circulation system. Furthermore, the protein is useful for coating natural or artificial collagen surfaces in order to render them nonadhesive for cells and prevent the activation of cells.

The invention relates to a fed-batch fermentation process which uses special host/vector systems for the purpose of efficiently forming recombinant proteins, in particular recombinant antibody molecules, preferably antibody fragments such as miniantibodies. Under the given conditions, the cells are able to grow at a maximum specific growth rate up to very high cell densities. After the recombinant product formation has been switched on, it is only the formed product which restricts growth; there is no growth restriction due to substrates or metabolic by-products. High space-time yields of recombinant proteins can be achieved in this manner.

Process for the preparation of recombinant proteins in E. coli by high cell density fermentation

The invention provides new immunoconjugates comprising a mono-clonal antibody or a fragment thereof specific for the human EGF-receptor molecule and a member of the chemokine family, preferably selected from the C-X-C family, e.g. lnterleukin-8 (IL-8). The immunoconjugates induce cytotoxic and chemotactic activity and are suitable for a targeted tumor therapy.

Immunoconjugates II

The present invention relates to novel and highly effective bispecific antibody fragments which recognize lymphocyte CD2 antigen and any variable tumor antigen. Moreover, the invention relates to two new monoclonal antibodies terms AICD2.M1 and AICD2.M2. A combination of these antibodies, whereby at least one of them is a bispecific antibody fragment, can be used successfully in tumor therapy and diagnostics.

Bispecific molecules recognizing lymphocyte antigen CD2 and tumor

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Ober-Ramstadt, Germany

Wolfgang Strittmatter