Boehringer Ingelheim International Gmbh

Boehringer Ingelheim Pharma Gmbh & Co Kg

Universitãt Stuttgart

Monilola Olayioye

Angelika Hausser

Michaela Strotbek

Lore Florin

Lisa Pieper

Till Wenger

Roland Kontermann

Meike Hutt

Hitto Kaufmann

Oliver Seifert

Michael Hust

Stefan Dübel

Eric Becker

Tim Fugmann

Jonas Zantow

Hitto Kaufman

Lisa Schmitt

The invention relates to the field of cell culture technology. It concerns the knockdown, using RNA interference, or gene knockout, of activating transcription factor 6 beta (ATF6B), or the combination of ceramide synthase 2 (CERS2) and TBC1 domain family member 20 (TBC1D20) proteins, which play central roles in the cellular secretion pathway. This downregulation leads to improved secretion of biopharmaceutically relevant products produced in mammalian cells. The invention specifically relates to mammalian cells having enhanced secretion of a recombinant therapeutic protein compared to a control cell, a method of producing said mammalian cell, a method for the production of a recombinant secreted therapeutic protein and the use of said mammalian cell for increasing the yield of a recombinant secreted therapeutic protein.

Mammalian cells for producing a secreted protein

The invention concerns the field of cell culture technology. It concerns RNA having a specific sequence, expression vectors encoding the RNA, production host cell lines comprising the RNA, and methods of producing recombinant biopharmaceutical products using engineered host cell with altered levels of the RNAs, such as small non-coding RNAs, preferably microRNAs (miRNAs). The invention also relates to engineered host cells with altered levels in one or more of the RNAs. Those cell lines have improved secretion and/or growth characteristics in comparison to control cell lines.

Cell engineering using MICRORNAs

The invention provides an antigen-binding protein that specifically binds to a conformational epitope formed by domain III & IV of human epidermal growth factor receptor 3 (HER3) and antigen-binding proteins which compete therewith for binding, as well as fusion protein or conjugate comprising these. The invention also provides nucleic acid molecule comprising a sequence encoding said antigen binding proteins, vectors comprising the nucleic acid, and cells and pharmaceuticals comprising the antigen binding protein, the fusion protein, the nucleic acid, or the vector. The invention also provides the antigen binding protein, the fusion protein or conjugate, the nucleic acid, the vector, the cell, or the pharmaceutical for use as a medicament. The invention further provides a method of inhibiting tumor growth or treating cancer, comprising administering a therapeutically effective amount of the antigen binding protein, the fusion protein or conjugate, the nucleic acid, the vector, the cell, or the pharmaceutical.

Antigen binding protein against HER3

The invention relates to the field of cell culture technology. It concerns the knockdown, using RNA interference, or gene knockout, of activating transcription factor 6 beta (ATF6B), or the combination of ceramide synthase 2 (CERS2) and TBC1 domain family member 20 (TBC1 D20) proteins, which play central roles in the cellular secretion pathway. This downregulation leads to improved secretion of biopharmaceutically relevant products produced in mammalian cells. The invention specifically relates to mammalian cells having enhanced secretion of a recombinant therapeutic protein compared to a control cell, a method of producing said mammalian cell, a method for the production of a recombinant secreted therapeutic protein and the use of said mammalian cell for increasing the yield of a recombinant secreted therapeutic protein.

The invention concerns the field of protein production and cell culture technology. CERT is identified as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT towards its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. The present invention shows that CERT in turn is critical for PKD activation and PKD dependent protein cargo transport to the plasma membrane. The interdependence of PKD and CERT is thus a key to the maintenance of Golgi membrane integrity and secretory transport.

Protein production

Growing community of inventors

Ulm, Germany

Monilola Olayioye