Glaxo Group Limited

Glaxosmithkline Intellectual Property Development Limited

Mark Uden

Alan Peter Lewis

Ekaterini Kotsopoulou

Ioannis Voulgaris

William John Kenneth Lewis

Xuan Hong

Austin Keith Doyle

Emma R Harding

Gary Brian Finka

Laura Maria Halo

Valeriu Damian

Michael Hoare

Andrew S Thomson

Adam Daniel McInally

Shugui Chen

Richard Kucia-Tran

Richard Priest

Hella Bosteels

Kayeleigh Farrow

Robyn Alexandra Emmins

The present invention relates to a method of producing a recombinant protein in a host cell comprising adding Polyethyleneimine (PEI) during cell culture. Addition of PEI to the cell culture as a fermentation enhancer can result in reducing the viscosity of the cell culture, and/or increasing the extracellular concentration of the recombinant protein, and/or reducing the duration of cell culture to the point of harvest or protein recovery.

Method of producing a recombinant protein

The present invention relates to methods of selecting, screening, engineering, making and modifying antibodies that have improved bioavailability upon subcutaneous administration to a human. Antibodies and variant antibodies with improved bioavailability upon subcutaneous administration to a human are also described.

Antibody variants

The present invention relates to variant antibodies and methods of generating said antibodies with a reduced level of binding to process impurities. In particular, the invention describes variant IgG4 antibodies which have been modified in the heavy chain constant region at any one or a combination of amino acids in the region between Kabat residues 203 and 256, wherein the variant IgG4 antibody has a reduced level of binding to host cell protein (HCP), compared to an unmodified IgG4 antibody. The invention also relates to compositions comprising said variant IgG4 antibodies.

Antibodies with reduced binding to process impurities

The present invention relates to a recombinant signal sequence derived from. The invention also relates to a fusion protein comprising the signal sequence, a recombinant protein and methods of producing the recombinant protein. The recombinant signal sequence can be used to provide a method for controlling the viscosity of the fermentation, and/or controlling basal (pre-induction) expression of the recombinant protein.

The present invention provides methods of reducing the levels of a titratable selectable pressure required, the number of amplification cycles, and the time taken to generate protein expressing cell lines by altering the codons of the desired open-reading-frames. Through the use of codon adaptation for this purpose the methods of the invention consistently provide sufficient yields in faster time frames saving many weeks in cell line development activities. Furthermore the methods of the invention also generate cell lines with lower concentrations of selection and amplification agent than previously achievable. Accordingly lower levels of selection and amplification marker in the final cells lines are observed.

Production methods

The invention provides methods for the rapid identification and selection of cell lines suitable for biopharmaceuticals production, which do no utilize animal derived components.

Method for selecting high producing cell lines

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Stevenage, United Kingdom

Mark Uden