Celltech Limited

Alusuisse Holdings A.g.

Celltech Therapeutics Limited

Aluguisse Holding A.g.

Mark Ian Cockett

Christopher Robert Bebbington

Geoffrey Thomas Yarranton

Raymond John Owens

Gregory Paul Winter

Lutz Riechmann

Mark William Bodmer

Andrew Mountain

Richard Harris Wilson

David John King

Gwynfor O Humphreys

Martin K Robinson

Celia A Caulcott

Edwina M Wright

The present invention provides a process and host cell for use in increasing the amount of a desired protein by a cell line. The process and the cell line use a first transcription unit containing a gene for a transactivator protein to control the transactivation of a second transcription unit such that the amount of the desired protein expression can be increased without adversely affecting the cell growth. Preferred transactivator proteins are derived from EIA.

Recombinant DNA method and host cells

Methods for preparing Fv fragments which lack linking polypeptides in eukaryotic cells are provided.

Method for producing Fv fragments in eukaryotic cells

The present invention relates to vectors useful for transforming a lymphoid cell line to glutamine independence. The vectors comprise an active glutamine synthetase (GS) gene as well as a heterologous gene of interest to be expressed. The preferred embodiments encompass vectors wherein the heterologous gene is expressed from a relatively strong promoter and the GS gene is expressed from a relatively weak promoter. In one example, the heterologous gene is operatively linked to the hCMV-MIE promoter and the GS gene is operatively linked to the SV40 early region promoter.

Recombinant DNA methods vectors and host cells

Recombinant DNA methods, vectors and host cells

The present invention provides a process and host cell for use in increasing the amount of a desired protein produced by a cell line. The process and the cell line use a first transcription unit containing a gene for a transactivator protein to control the transactivation of a second transcription unit such that the amount of desired protein expression can be increased without affecting adversely cell growth. Preferred transactivator proteins are derived from E1A.

Transactivation method of regulating foreign gene expression

A multivalent antigen-binding protein comprises a first Fv fragment bound to at least one further Fv fragment by a connecting structure which links the Fv fragments to each other but which maintains them spaced apart such that the proteins are capable of binding to adjacent antigenic determinants. Typically the connecting structure comprises a spacing polypeptide sequence, which may be about 3 to 16 amino acids in length, connected to a linkage unit which may be a synthetic chemical linker, e.g., a maleimide linker, or is a polypeptide sequence leading from the spacing sequence. In a particularly preferred embodiment, the multivalent antigen binding protein comprises a VH domain having attached to its C-terminal end a V-C joining sequence and an antibody hinge sequence. Preferably one or more of the Fv fragments is a single chain Fv (scFv). The proteins are preferably prepared by recombinant DNA techniques and are useful for in vivo therapeutic and especially diagnostic applications.

Multivalent antigen-binding proteins

There is described a method for obtaining a eukaryotic cell containing in its DNA multiple copies of a GS gene, comprising: transforming a eukaryotic glutamine auxotroph with a GS gene; selecting transformant cells containing the GS gene; and culturing the selected transformant cells in a medium which lacks glutamine or in which the amount of glutamine is progressively depleted, the GS gene being of a character such that, or the conditions employed during the culturing step being such that, the GS gene is so weakly transcribed that the cells in which the GS gene has been amplified are selected.

Recombinant DNA method

A new class of DNA vectors, each comprising two replication systems; a first origin of replication resulting in a low copy number and stable inheritance of the plasmid, and a second, high copy number, origin of replication at which replication is directly controllable such that, when host cells carrying the vector are propagated under a first set of conditions, replication takes mainly from the low copy number origin, and that when said cells are propagated under a second set of conditions, replication takes place also from the high copy number origin to produce a high yield of gene product. The controllable origin of replication may be under the control of a natural promoter of RNA transcription or a substitute promoter such as the PL promoter or lac promoter.

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Winnersh, United Kingdom

Geoffrey Thomas Yarranton