Boehringer Ingelheim Pharma Gmbh & Co Kg

Boehringer Ingelheim International Gmbh

Lore Florin

Hitto Kaufmann

Eric Becker

Monilola Olayioye

Thomas Krieg

Angelika Hausser

Sanjaya Singh

Holger Rosenbrock

Michael Dziegelewski

Juergen Fieder

Remko Alexander Bakker

Haiguang Xiao

Sarah Low

Vladimir H Voynov

Sathyadevi Venkataramani

Sebastian Bandholtz

Peter Michael Benz

Michaela Strotbek

Cynthia Hess Kenny

Heiko Friedrich Stahl

Rolf Herrmann

Hitto Kaufman

Joey M Studts

Rebecca Bischoff

Jüergen Fieder

Melanie Briegel

Tim Fugmann

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 present invention relates to novel agonistic anti-TrkB antibodies and therapeutic and diagnostic methods and compositions for using the same.

Anti-TrkB antibodies

The invention concerns the field of cell culture technology. The invention describes production host cell lines comprising vector constructs comprising a CERT S132 A expression cassette. Those cell lines have improved growth characteristics and high CERT S132A expression levels. The invention especially concerns two cell lines deposited with the DSMZ under the number DSM ACC2989 (CHO/CERT 2.20) and DSM AC-C2990 (CHO/CERT 2.41). The invention further concerns a method of generating such preferred production host cells and a method of producing proteins using the two cell lines deposited with the DSMZ under the number DSM ACC2989 (CHO/CERT 2.20) and DSM ACC2990 (CHO/CERT 2.41).

CHO/CERT cell lines

The invention concerns the field of cell culture technology. The invention describes production host cell lines comprising vector constructs comprising a DHFR expression cassette. Those cell lines have improved growth characteristics in comparison to DHFR-deficient or DHFR-reduced cell lines such as CHO DG44 and CHO DUKX-B11. The invention especially concerns two cell lines, a representative of each cell line is deposited with the DSMZ under the number DSM ACC2909 (CHOpper&#xae; Discovery) and DSM ACC2910 (CHOpper&#xae; Standard). The invention further concerns a method of producing proteins using the cells generated by the described method.

Production host cell lines

The present invention refers to the area of cell culture technology and relates to methods for multiplying/cloning cells, preferably cell lines, which are important to the production of biopharmaceuticals. The invention further relates to methods for manufacturing proteins and to the use of cells extracted and multiplied through single cell sorting and to media compositions that enable a multiplication of single cells. Through the use of albumin-producing, preferably HSA-producing, cells as feeder cells for the conditioning of medium or as host cells, the recloning efficiency and thereby the quantity of clones obtained can be significantly increased. A combination of these approaches is also possible. Through the use of albumin-producing, preferably HSA-producing, cells, an increase in the recloning efficiency can be achieved in serum-free and/or insulin-free medium as well, and in different cell types.

Use of HSA-producing cells

The present invention relates to the field of cell culture technology and relates to methods of replicating/cloning cells, preferably cell lines which are important for the production of biopharmaceuticals. The invention also relates to methods of preparing proteins using cells that have been obtained and replicated by single cell deposition and compositions which make it possible to replicate individual cells. By using IGF particularly in conjunction with HSA in the culture medium after recloning, the recloning efficiency and hence the quantity of clones obtained can be increased significantly.

Method for increasing recloning efficiency

The invention concerns the field of cell culture technology. It concerns a method of improving cell growth, especially the growth of biopharmaceutical producer host cells. The invention further concerns a method of producing proteins using the cells generated by the described method.

Cell growth

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

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Biberach, Germany

Lore Florin