University Of Zürich

Morphosys Ag

Other

Merck Patent Gesellschaft

Andreas Pl&uuml;ckthun

Peter Pack

Achim Knappik

Liming Ge

Simon Moroney

Lutz Jermutus

Jozef Hanes

Wolfgang Strittmatter

Annemarie Honegger

Siegfried Matzku

Uwe Horn

Dieter Riesenberg

Marian Kujau

Rolf Wenderoth

Anke Krebber

Lars Nieba

Hendrick Bothmann

Uwe Kn&uuml;peer

The present invention relates to the modification of immunoglobulin superfamily (IgSF) domains, IgSF fragments and fusion proteins thereof, especially to the modification of antibody derivatives, so as to improve their solubility, and hence the yield, and ease of handling. The inventors have found that this can be achieved by making the region which comprised the interface with domains adjoined to said IgSF domain in a larger fragment or a full IgSF protein, and which becomes exposed in the IgSF domain, more hydrophilic by modification. The present invention describes DNA sequences encoding modified IgSF domains or fragments and fusion proteins thereof, vectors and hosts containing these DNA sequences, IgSF domains or fragments or fusion proteins obtainable by expressing said DNA sequences in suitable expression systems, and a method for modifying IgSF domains, so as to improve their solubility, expressibility and ease of handling.

Immunoglobulin superfamily domains and fragments with increased solubility

The present invention relates to synthetic DNA sequences which encode one or more collections of homologous proteins/(poly)peptides, and methods for generating and applying libraries of these DNA sequences. In particular, the invention relates to the preparation of a library of human-derived antibody genes by the use of synthetic consensus sequences which cover the structural repertoire of antibodies encoded in the human genome. Furthermore, the invention relates to the use of a single consensus antibody gene as a universal framework for highly diverse antibody libraries.

Protein/(poly)peptide libraries

The present invention relates to a method for obtaining nucleic acid sequences encoding (poly)peptides which increase the expression yields of periplasmic proteins in functional form upon co-expression of said (poly)peptides and said periplasmic proteins. The invention also provides a method for the identification of said (poly)peptides. Furthermore, the present invention relates to a method for increasing the expression yields of periplasmic proteins in functional form by co-expressing (poly)peptides, for example Skp, FkpA, or a homolog of Skp or FkpA, in bacteria.

Methods for obtaining, identifying and applying nucleic acid sequences and (poly)peptides which increase the expression yields of periplasmic proteins in functional form

The present invention relates to methods for identifying nucleic acid molecules encoding (poly)peptides that interact with target molecules. The method of the present invention is particularly characterized by an in vitro translation step under conditions that allow formation of polysomes in the presence of antisense oligonucleotides complementary to the tag-coding sequence of ssrA-RNA. The present invention further relates to kits that are useful for carrying out the method of the invention.

Polysome display in the absence of functional ssrA-RNA

The invention relates to a fed-batch fermentation process which uses special host/vector systems for the purpose of efficiently forming recombinant proteins, in particular recombinant antibody molecules, preferably antibody fragments such as miniantibodies. Under the given conditions, the cells are able to grow at a maximum specific growth rate up to very high cell densities. After the recombinant product formation has been switched on, it is only the formed product which restricts growth; there is no growth restriction due to substrates or metabolic by-products. High space-time yields of recombinant proteins can be achieved in this manner.

Process for the preparation of recombinant proteins in E. coli by high cell density fermentation

Growing community of inventors

Zurich, Switzerland

Andreas Plückthun

Growing community of inventors

Zurich, Switzerland

Andreas Pl&uuml;ckthun

Andreas Plückthun