Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The invention pertains to an expression vector or a combination of at least two expression vectors comprising at least (a) a polynucleotide encoding a product of interest or an insertion site for incorporating a polynucleotide encoding a product of interest; (b) a polynucleotide encoding a first selectable marker (sm I); (c) a polynucleotide encoding a second selectable marker (sm II), which is different from the first selectable marker (sm I), wherein the activity of the selectable marker (sm I) or (sm II) is at least partially influenced by the activity of the other selectable marker and wherein the selectable markers (sm I) and (sm II) are involved in the folate metabolism. Also provided are suitable host cells, selection methods and methods for producing polypeptides with high yield.

Abstract: The present invention relates to IL-15/IL-15R? heterodimer produced in a CHO cell line, and method of producing the heterodimer and method of treatment using the heterodimer.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The invention pertains to an expression vector or a combination of at least two expression vectors comprising at least (a) a polynucleotide encoding a product of interest or an insertion site for incorporating a polynucleotide encoding a product of interest; (b) a polynucleotide encoding a first selectable marker (sm I); (c) a polynucleotide encoding a second selectable marker (sm II), which is different from the first selectable marker (sm I), wherein the activity of the selectable marker (sm I) or (sm II) is at least partially influenced by the activity of the other selectable marker and wherein the selectable markers (sm I) and (sm II) are involved in the folate metabolism. Also provided are suitable host cells, selection methods and methods for producing polypeptides with high yield.

Abstract: 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.

Abstract: The invention pertains to an expression vector or a combination of at least two expression vectors comprising at least (a) a polynucleotide encoding a product of interest or an insertion site for incorporating a polynucleotide encoding a product of interest; (b) a polynucleotide encoding a first selectable marker (sm I); (c) a polynucleotide encoding a second selectable marker (sm II), which is different from the first selectable marker (sm I), wherein the activity of the selectable marker (sm I) or (sm II) is at least partially influenced by the activity of the other selectable marker and wherein the selectable markers (sm I) and (sm II) are involved in the folate metabolism. Also provided are suitable host cells, selection methods and methods for producing polypeptides with high yield.

Abstract: The present invention inter alia pertains to a method for generating or selecting a eukaryotic host cell expressing a desired level of a polypeptide of interest, comprising: a) providing a plurality of eukaryotic host cells comprising a heterologous nucleic acid comprising at least one cassette (Cas-POI) comprising at least a first polynucleotide (Pn-POI) encoding the polypeptide of interest, at least one stop codon downstream of the first polynucleotide, and a second polynucleotide downstream of the stop codon encoding an immunoglobulin transmembrane anchor or a functional variant thereof; b) cultivating the eukaryotic host cells 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 comprising the immunoglobulin transmembrane anchor or a functional variant thereof, wherein said fusion polypeptide is being displayed on the surface of said host cell; c) selecting at least one eukaryotic host cell based upon the pre

Abstract: 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.

Abstract: The invention pertains to an expression vector or a combination of at least two expression vectors comprising at least (a) a polynucleotide encoding a product of interest or an insertion site for incorporating a polynucleotide encoding a product of interest; (b) a polynucleotide encoding a first selectable marker (sm I); (c) a polynucleotide encoding a second selectable marker (sm II), which is different from the first selectable marker (sm I), wherein the activity of the selectable marker (sm I) or (sm II) is at least partially influenced by the activity of the other selectable marker and wherein the selectable markers (sm I) and (sm II) are involved in the folate metabolism. Also provided are suitable host cells, selection methods and methods for producing polypeptides with high yield.

Abstract: 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.

Abstract: 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.