Merck Patent Gmbh

Stefan Becker

Bjoern Hock

Laura Rhiel

Harald Kolmar

Ralf Guenther

Gordana Wozniak-Knopp

Daniel Helman

Mira Toister-Achituv

Florian Rüker

Alec Gross

Sylvia Dietrich

Martin Empting

Simon Krah

Christian Schroeter

Ralph Guenther

Tim Heiseler

Alexander Maass

Stefan Zielonka

Alec W Gross

The present invention provides a method for generating bispecific shark variable antibody domains (vNAR domains) and uses thereof. The present invention further provides fusion proteins comprising the inventive bispecific vNAR domains as well as polynucleotide libraries for use in the generation of the inventive bi-specific vNARs. Furthermore, the invention provides pharmaceutical compositions comprising the inventive bispecific vNARs or fusion proteins comprising bi-specific vNAR domains for use in the treatment of pathological conditions in an individual. The invention also provides kits of parts comprising the bispecific vNAR domains or fusion proteins.

Methods for generating bispecific shark variable antibody domains and use thereof

The invention provides for a domain-exchanged antibody comprising a light chain (LC) composed of VL-CH3, and a heavy chain (HC) comprising VH-CH3-CH2-CH3, wherein the VL-CH3 of the LC is dimerising with the VH-CH3 of the HC thereby forming a domain-exchanged LC/HC dimer comprising a CH3LC/CH3HC domain pair, and means and method for producing the same.

Domain-exchanged antibody

The present invention provides methods for the non-covalent surface display of proteins of interest (POI), in particular for Fc-domain containing proteins such as antibodies. The inventive method may be used to screen and select proteins of interest of a desired phenotype. The present invention further discloses polynucleotides and proteins and methods of producing the same, which may be used in carrying out the inventive method.

Methods for non-covalent Fc-domain-containing protein display on the surface of cells and methods of screening thereof

The invention relates to anti-TNF&#x3b1; antibodies which are engineered to exhibit a pH-sensitive antigen binding. The invention is preferably directed to anti-TNF&#x3b1; antibody adalimumab (Humira&#xae;) or biologically active variants and fragments thereof, wherein the original adalimumab antibody or variant or fragment thereof is engineered by modifications of amino acid sequence within the variable regions. Specifically, the invention relates to adalimumab or biologically active variants or fragments thereof, wherein the CDR domains are modified by replacing one or more amino acid residues by histidine residues.

Anti-TNF&#x3b1; antibodies with pH-dependent antigen binding for improved target clearence

The invention relates to a method for the production and non-covalent surface display of antibodies and derived fragments as well as molecule libraries based thereon on the surface ofcells. The non-covalent manner of the surface display renders possible the selection of specific variants by means of high throughput screening and the subsequent switchable secretion of the selected binding molecule into the culture supernatant for biochemical characterization.

Method of producing secretable antibodies by expression in saccharomyces cerevisiae

A generally applicable method for the selective covalent attachment of a reporter molecule to a replicating entity that allows one to obtain specific binders from a single round of library screening is disclosed. For example, selective biotinylation of phage particles and yeast cells displaying a binder to any given target can be achieved via application of a coupled enzyme reaction that includes a peroxidase, an oxidase and a catalase.

General strategy for antibody library screening

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Darmstadt, Germany

Stefan Becker