Merck Patent Gmbh

Merck Gmbh

Uwe Hofmann

Wolfgang Strittmatter

Bernhard Scheuble

Zisi Fotev

Johannes Gleitz

Christopher Barnes

Siegfried Matzku

Detlef Güssow

Jürgen Hemberger

Matthias Frech

Andree Blaukat

Bjoern Hock

Maria Kordowicz

Tanja Henzler

Ilka Von Hoegen

Carlota-Silvia Jaggle

Tadeusz Pacuszka

Andrzej Gardas

Britta Sundermann

Oliver Wilbert

Jörg Stadlmüller

J&uuml;rgen Hemberger

Detlef G&uuml;ssow

The present invention relates to methods for measuring the autophosphorylation of one or more tyrosine kinases and use of such methods in profiling kinase inhibitors and activators. As a representative example, the method comprises inducing kinase autophosphorylation activity in cells in presence and in absence of a kinase inhibitor, lysing the cells, capturing the tyrosine kinase in the cell lysate by adding a plurality of tyrosine kinase specific binding proteins which are associated with unique dyes, adding a phosphotyrosine specific antibody tagged with a marker which is distinguishable from the unique dyes, and identifying the autophosphorylated tyrosine kinase by detecting the unique dye and the marker. Alternately, the tyrosine kinases themselves could be coupled to the unique dyes. The present invention also relates to kits and compositions for carrying out the above-described methods.

Method for measuring tyrosine kinase phosphorylation

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 the isolation, purification and characterization of a hyaluronidase which derives from the tropical leech. Therefore, according to this invention, the enzyme was called 'manillase'. The invention is furthermore concerned with the recombinant method of production of manillase which includes the disclosure of DNA and amino acid sequences as well as of expression vectors and host systems. Finally, the invention relates to the use of manillase for therapeutic purposes, for example, for the treatment of myocardial diseases, thrombotic events and tumors.

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Seripancrin polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing Seripancrin polypeptides and polynucleotides in diagnostic assays.

Seripancrin

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.

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Alsbach, Germany

Uwe Hofmann