Genentech, Inc.

Genetech, Inc.

F. Hoffmann-la Roche Ag

Tina M Etcheverry

Thomas Ryll

Avi J Ashkenazi

Phillip W Berman

Ronald A Hitzeman

David Brousseau

Wolfgang Richter

Thomas Schreitmüller

The present invention relates to novel process for the preparation of glycoproteins by mammalian-cell culture wherein the sialic acid content of the glycoprotein' produced is controlled over a broad range of values by manipulating the cell culture environment. The invention provides for processes in which the sialic acid content of the glycoprotein is modified by changes in cell culture parameters which affect cell specific productivity. Preferred embodiments of the invention include cell culture processes in the osmolality of the cell culture is controlled as well as the concentration of a transcription enhancer during the production phase of the cell culture. The invention further provides for novel preparations of-soluble type 1 tumor necrosis factor immunoglobulin G1 and their uses in the treatment of inflammatory or immune related disorders.

Mammalian cell culture process

DNA constructs, host cells and production methods are disclosed for the expression and recovery of polypeptides, especially those altered to have one or more glycosylation sites added or deleted. The DNA constructs, host cells and methods provided herein employ a DNA segment corresponding to a mammalian tissue plasminogen activator signal and/or pro peptide.

Protein secretion

The present invention relates to novel process for the preparation of glycoproteins by mammalian cell culture wherein the sialic acid content of the glycoprotein produced is controlled over a broad range of values by manipulating the cell culture environment. The invention provides for processes in which the sialic acid content of the glycoprotein is modified by changes in cell culture parameters which affect cell specific productivity. Preferred embodiments of the invention include cell culture processes in the osmolality of the cell culture is controlled as well as the concentration of a transcription enhancer during the production phase of the cell culture. The invention further provides for novel preparations of soluble type 1 tumor necrosis factor immunoglobulin G1 and their uses in the treatment of inflammatory or immune related disorders.

Human tumor necrosis factor&mdash;immunoglobulin(TNFR1-IgG1) chimera composition

Mammalian cell culture process for producing a tumor necrosis factor

Metallothionein transcription control sequences, promoters or inducing regions, free of DNA encoding metallothionein, are used to inducibly express genes encoding polypeptides of interest. Vectors and host expression systems using the transciption control sequences, promoters and/or inducing regions are provided.

Metallothionein transcription control sequences and use thereof

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Berkeley, CA, United States of America

Tina M Etcheverry