University Of Zürich

Unversität Zürich

Morphosys Ag

Odyssey Thera Inc.

Morphosys Gesellschaft Fur Proteinoptimerung Mbh

Andreas Plückthun

Michael Tobias Stumpp

Patrik Forrer

Annemarie Honegger

Hans Kaspar Binz

Jörg Willuda

Stephen William Watson Michnick

Peter Pack

Achim Knappik

Daniel Steiner

Liming Ge

Joelle Nina Pelletier

Simon Moroney

Katja M Arndt

Daniel Scott

Christian Jost

Hans Kasper Binz

Rastislav Tamaskovic

Fabio Parmeggiani

Patrick Forrer

Riccardo Pellarin

Joerg Willuda

Anders Peter Larsen

Gautham Varadamsetty

Christian Schneider

Klaus Krebber

Martin Schwill

Marco Schutz

The invention relates to a method for selecting a sequence set from a library of expressed nucleic acid sequences, wherein cells are provided, each cell comprises an expressed nucleic acid sequence expressed as a target protein. The cells are encapsulated by treating them with a cationic polysaccharide and subsequently treating them with an anionic polysaccharide, yielding encapsulated cells, perforating the membrane of the encapsulated cells, yielding solubilized compartments, contacting them with a ligand to said target protein, the ligand bearing a detectable label, and selecting a subset of solubilized compartments as a function of detectable label and isolating the expressed nucleic acid sequences from the selection as a selected sequence set.

Cellular high throughput encapsulation for screening or selection

The invention relates to a bispecific HER2-targeting agent comprising a.) a first polypeptide ligand that binds to HER2 extracellular domain 1, b.) a second polypeptide ligand that binds to HER2 extracellular domain 4 and c.) a linker covalently attaching said first polypeptide ligand to said second polypeptide ligand.

Bispecific HER2 ligands for cancer therapy

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

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

Phage display using cotranslational translocation of fusion polypeptides

The present invention relates to a method of identifying one or more genes encoding one or more proteins having an optimized property. In particular, the method comprises expressing a collection of genes and screening for a desired property, identifying a plurality of genes having the desired property, and replacing one or more one or more sub-sequences of each of said genes with a different, compatible genetic sub-sequence, and screening again in order to identify genes encoding proteins having an optimized property.

Protein (poly)peptides libraries

The present invention relates to a method for stabilizing chimeric immunoglobulins or immunoglobulin fragments. Furthermore, the invention also provides a stabilized anti-EGP-2 scFv fragment.

Method for the stabilization of chimeric immunoglobulins or immunoglobulin fragments, and stabilized anti-EGP-2 scFv fragment

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 describes a rapid and efficient in vivo library-versus-library screening strategy for identifying optimally interacting pairs of heterodimerizing polypeptides. It allows for the screening of a protein library against a second protein library and therefore finds numerous applications in the study of protein-protein interactions. Two leucine zipper libraries, semi-randomized at the positions adjacent to the hydrophobic core, were genetically fused to either one of two designed fragments of the enzyme murine dihydrofolate reductase (mDHFR), and cotransformed into. Interaction between the library polypeptides was required for reconstitution of the enzymatic activity of mDHFR, allowing bacterial growth. Using more weakly associating mDHFR fragments, we increased the stringency of selection. We applied these selection processes to a library-versus-library sample of 2.0&#xd7;10combinations, and selected a novel leucine zipper pair which may be appropriate for use in further in vivo heterodimerization strategies.

[object Object]

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.

Collection of repeat proteins comprising repeat modules

Growing community of inventors

Zurich, Switzerland

Andreas Plückthun