Novartis Ag

Mab Factory Gmbh

Thomas Jostock

Hans-Peter Knopf

Burkhard Wilms

David Jonathan Glass

Christian Menzel

Anett Ritter

Michael Otto Bardroff

Stefan Dübel

Holger Laux

Audrey Nommay

Yehuda G Assaraf

Mara Fornaro

Jiri Kovarik

Maximilian Woisetschlaeger

Christian Graf

Sandrine Romand

Thomas Schirrmann

Tina Buch

Daniel Heitmann

Dhavalkumar Patel

Rolf Koehler

Stephen John Oliver

Audrey Josiane Nommay

The invention relates to bivalent bispecific monoclonal antibodies (bbmAb) or variants thereof, and methods of manufacturing such antibodies by co-expressing modified Fc-mutated derivatives of two different monoclonal antibodies in mammalian cell lines.

Method of manufacturing bispecific antibodies, bispecific antibodies and therapeutic use of such antibodies

The disclosure is directed to an expression vector or a combination of at least two expression vectors for producing a polypeptide of interest, the vector or vectors comprising a polynucleotide encoding a mutated folate receptor as a selectable marker. The disclosure also relates to host cells, selection methods and methods for producing polypeptides with high yield.

Selection vectors and methods of selecting eukaryotic host cells

The disclosure pertains to novel eukaryotic cell suitable for recombinant production of a product of interest, wherein the genome of the host cell is altered so that the effect of protein FAM60A is impaired in said cell, e.g. by reducing or eliminating functional expression of gene FAM60A thereby improving the stability characteristics. Furthermore, the present disclosure provides associated technologies wherein such host cells are used in recombinant production technologies.

Eukaryotic cells and methods for recombinantly expressing a product of interest

The disclosure pertains to novel eukaryotic cell suitable for recombinant production of a product of interest, wherein the effect of the expression product of an endogenous gene C12orf35 is impaired in said cell, thereby increasing their productivity when recombinantly expressing a polypeptide of interest. Furthermore, the present disclosure provides associated technologies wherein such host cells are used in recombinant production technologies.

The invention pertains to an expression vector or a combination of at least two expression vectors comprising at least

Expression vector system comprising two selection markers

The present invention relates to a novel selection system for use in a eukaryotic cell culture process and for expression of a recombinant product of interest. The selection system is based on the introduction of an exogenous functional membrane-bound folate receptor gene together with the polynucleotide or gene encoding the product of interest into a eukaryotic cell and can be widely utilized with eukaryotic cells for which cellular viability is dependent upon folic acid uptake.

Organic compounds

A method for selecting mammalian host cells that express a polypeptide of interest with high yield is described. The host cells comprise an expression cassette comprising at least a first polynucleotide encoding the polypeptide of interest, at least one leaky stop codon downstream of the first polynucleotide, and a second polynucleotide downstream of the leaky stop codon encoding an immunoglobulin transmembrane anchor. The host cells are cultivated to allow expression of the polypeptide of interest such that at least a portion of the polypeptide of interest is expressed as a fusion polypeptide that is displayed on the cell surface. The cells are selected based upon the presence or amount of the displayed fusion polypeptide. Also provided are methods for producing a polypeptide that employ a respective selection to identify high expressing host cells.

Cell surface display of polypeptide isoforms by stop codon readthrough

The invention relates to methods for the production of therapeutic proteins in mammalian cells. In one embodiment, the method comprises producing a therapeutic protein such as IGF-1 in a mammalian cell endogenously expressing a cognate receptor of said recombinant therapeutic protein and wherein binding of said therapeutic protein to said cognate receptor results in a low titer of the therapeutic protein, the method comprising with a mammalian cell being deficient in the expression of the cognate receptor of said therapeutic protein and being transformed with an expression vector comprising a nucleic acid molecule encoding the therapeutic protein: a. Cultivating said cell under conditions allowing the expression of the therapeutic protein; and b. Harvesting the therapeutic protein from the mammalian cell cultivated in step a, wherein said mammalian cell produces at least 1.5 fold more therapeutic protein than a cell in which the expression of the cognate receptor has not been so modified.

Production of therapeutic proteins in genetically modified mammalian cells

The application describes a method of selecting mammalian host cells that express a polypeptide of interest with high yield. The host cells contain an expression cassette with a first polynucleotide encoding a polypeptide of interest, at least one leaky stop codon located downstream of the first polynucleotide and a second polynucleotide located downstream of the leaky codon encoding an immunoglobulin transmembrane anchor comprising a cytoplasmic domain. The host cells are cultivated to allow expression of the polypeptide of interest such that some of the polypeptides of interest are expressed as fusion proteins displayed on the cell surface. High producing cells are then selected based on the presence or amount of the displayed fusion polypeptides.

The present invention pertains to a method for selecting at least one eukaryotic host cell expressing a product of interest. The method entails providing a plurality of host cells which are dependent upon folate uptake and contain polynucleotides encoding for the product of interest and a DHFR enzyme. The cells are cultured in a selective culture medium containing at least an inhibitor of DHFR and folate. The expressed cells are then selected.

Methods for selecting eukaryotic cells expressing a heterologous protein

The invention pertains to a method for selecting at least one eukaryotic host cell expressing a product of interest, comprising Also provided is a method for expressing a product of interest which is based on host cells selected by said method and a cell culture medium.

Growing community of inventors

Neuenburg am Rhein, Germany

Thomas Jostock