Deutsches Krebsforschungszentrum

Heidelberg Biotech Gmbh

Ruprecht-Karls-Universitat Heidelberg

Jürgen Debus

Kashi Javaherian

Frederik Giesel

Amir Abdollahi

Rainer Neumann

Cheng Zhou

Marc MÜNTER

The present invention pertains to a method for producing a protein oligomer comprising at least two, and preferably three heterodimeric human NC-I-Fc proteins, the method comprising: a) culturing a host cell expressing (i) a fusion protein comprising, from N- to C-terminus, human NC-1 from collagen 18 fused to human IgGI Fc with 'knob' mutations, or human IgGI Fc with “knob” mutations fused to human NC-1 from collagen 18, and (ii) human IgGI Fc with “hole” mutations, under conditions which allow the formation of a protein oligomer comprising at least two, and preferably three heterodimeric human NC-1-Fc proteins, and wherein the fusion protein of (i) and the human IgGI Fc with “hole” mutations of (ii) are expressed in a ratio of 2:1 or higher, and b) obtaining the protein oligomer comprising at least two, and preferably three heterodimeric human NC-1-Fc proteins.

Means and methods for the treatment of angiogenesis-, fibrosis- and cancer-related diseases with protein oligomers comprising NC-1-Fc

The present invention is concerned with a protein oligomer comprising (i) at least two NC-monomers of collagen 18 or (ii) at least two endostatin domains of collagen 18 or (iii) at least two N-terminal peptides of the collagen 18 endostatin domain, for use in treating, ameliorating or preventing fibrosis or a fibrosis-associated disease, a vascular endothelial growth factor (VEGF)-related disease or a matrix metalloproteinase (MMP)-related disease. The invention further relates to the mentioned protein oligomer for use for detecting and/or diagnosing fibrosis or a fibrosis-associated disease, a vascular endothelial growth factor (VEGF)-related disease or a matrix metalloproteinase (MMP)-related disease.

Means and methods for treating and diagnosing fibrosis or fibrosis-associated diseases

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Heidelberg, Germany

Jürgen Debus