Molecular Partners Ag

University Of Zürich

Unversität Zürich

Molecular Partner Ag

Michael Tobias Stumpp

Patrik Forrer

Hans Kaspar Binz

Daniel Steiner

Andreas Plückthun

Frieder W Merz

Douglas Phillips

Ignacio Dolado

Ivo Sonderegger

Maya Gulotti-Georgieva

Talitha Bakker

Johan Abram Saliba

Hans Kasper Binz

Fabio Parmeggiani

Patrick Forrer

Gautham Varadamsetty

Anders Peter Larsen

Riccardo Pellarin

Andreas PLÜCKTHUN

New designed ankyrin repeat domains with binding specificity for serum albumin, recombinant binding proteins comprising at least two designed ankyrin repeat domains with binding specificity for serum albumin, as well as recombinant binding proteins comprising at least one designed ankyrin repeat domain with binding specificity for hepatocyte growth factor (HGF), at least one designed ankyrin repeat domain with binding specificity for vascular endothelial growth factor (VEGF-A), and at least two designed ankyrin repeat domain with binding specificity for serum albumin are described, as well as nucleic acids encoding such designed ankyrin repeat domains and recombinant binding proteins, pharmaceutical compositions comprising such designed ankyrin repeat domains, recombinant binding proteins or nucleic acids and the use of such designed ankyrin repeat domains, recombinant binding proteins, nucleic acids or pharmaceutical compositions in the treatment of diseases.

Recombinant binding proteins and their use

The present invention relates to binding proteins specific for VEGF-A, in particular to recombinant binding proteins comprising a polyethylene glycol moiety and a binding domain, which inhibits VEGF-Axxx binding to VEGFR-2. Examples of such recombinant binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity, and a polyethylene glycol moiety. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.

Modified binding proteins inhibiting the VEGF-A receptor interaction

A repeat protein from a collection of repeat proteins, wherein each repeat protein of said collection comprises a repeat domain, which comprises a set of consecutive repeat modules, wherein the repeat modules have the same fold and stack tightly to create a superhelical structure having a joint hydrophobic core, wherein each of the repeat modules is derived from one or more repeat units and wherein the repeat units comprise framework residues, which contribute to the folding topology of the repeat unit or contribute to an interaction with a neighboring repeat unit, and target interaction residues, which contribute to an interaction with a target substance, wherein the repeat proteins of the collection differ from other repeat proteins in the collection in at least one amino acid position of the repeat modules is described as are related pharmaceuticals and nucleic acid molecules.

Repeat protein from collection of repeat proteins comprising repeat modules

Recombinant proteins that simultaneously bind HGF, VEGF-A and serum albumin, comprising ankyrin repeat domains

The present invention relates to a filamentous phage display method wherein the polypeptides of interest displayed on the phage particle are cotranslationally translocated across the cytoplasmic membrane of Gram-negative bacteria based on the signal recognition particle pathway. This method is particularly suitable for polypeptides, which are known to be difficult to display on phages, and for proteins of cDNA libraries and other combinatorial libraries, in particular when derived from very fast folding, stable protein scaffolds. The invention further relates to phage or phagemid vectors useful in the method comprising a gene construct coding for a fusion polypeptide comprising the polypeptide to be displayed on the phage particle and an N-terminal signal sequence promoting cotranslational translocation.

Phage display using contranslational translocation of fusion polypeptides

The invention relates to collections of target-specific designed binding proteins based on armadillo repeat proteins, and to a method of generating them. Designed armadillo repeat proteins are based on consensus sequences of single armadillo repeat units. These repeat proteins can be used as scaffolds for peptide recognition. Such a scaffold provides a binding mode that is in principle the same for every small recognizable unit, e.g. an amino acid or dipeptide, allowing a precise and modular recognition of a peptide in extended conformation. The method allows to generate a series of modules recognizing these simple units, and to combine such building blocks to create a binding site for any desired peptide target without performing additional selections.

Designed armadillo repeat proteins

The present invention relates to binding proteins specific for Vascular Endothelial Growth Factor A (VEGF-A), in particular to recombinant binding proteins comprising a polyethylene glycol moiety and a binding domain, which inhibits VEGF-Axxx (wherein xxx denotes the amino acid length of the VEGF-A mature protein) binding to Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2). Examples of such recombinant binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity, and a polyethylene glycol moiety. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.

The present invention relates to binding proteins specific for VEGF-A, in particular to recombinant binding proteins comprising a binding domain, which inhibits VEGF-Axxx binding to VEGFR-2. Examples of such binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.

Binding proteins inhibiting the VEGF-A receptor interaction

Phage display using cotranslational translocation of fusion polypeptides

A collection of repeat proteins, each repeat protein comprising a repeat domain, which comprises a set of consecutive repeat modules, wherein each of the repeat modules is derived from one or more repeat units and wherein the repeat units comprise framework residues, which contribute to the folding topology of the repeat unit or contribute to an interaction with a neighboring repeat unit, and target interaction residues, which contribute to an interaction with a target substance, wherein the repeat proteins differ from other repeat proteins in the collection in at least one amino acid position of the repeat modules is described.

Collections of repeat proteins comprising repeat modules

The present invention relates to collections of repeat proteins comprising repeat modules which are derived from one or more repeat units of a family of naturally occurring repeat proteins, to collections of nucleic acid molecules encoding said repeat proteins, to methods for the constructions and application of such collections and to individual members of such collections.

Growing community of inventors

Geroldswil, Switzerland

Michael Tobias Stumpp