Wyeth

Wyeth Research Ireland Limited

Pfizer Corporation

Pfizer Ireland Pharmaceuticals

Wenge Wang

Daniel T Lasko

Yen-Tung Luan

Denis Drapeau

Daniel R Lasko

James R Mercer

Leo J Letendre

Tao He

Xiaotian Zhong

Amarnauth Shastrie Prashad

Ronald William Kriz

Jose Manuel Gomes

Will Somers

Gregory Walter Hiller

Ryan Nolan

Yen Tung Luan

Terry Cardoza

Gregg Nyberg

Paul Thoday

Judy Chou

Leo Joseph Letendre

Methods of producing a protein in cell culture comprising an anti-senescence compound, such as the antioxidant carnosine, are provided. According to teachings of the present invention, cells grown in a cell culture medium comprising an anti-senescence compound exhibit increased viability and productivity. Furthermore, cell cultures grown in the presence of an anti-senescence compound exhibit decreased levels of high molecular weight aggregates in the cell culture medium.

Methods of protein production using anti-senescence compounds

An antibody production process in mammalian cells in which engineered unpaired cysteine residues are post-translationally modified and capped with particular chemical entities, which capped antibodies are well suited to further site-specific conjugation steps to form antibody-drug conjugates (ADCs) or protein drug conjugates; ADCs produced using these capped antibodies including in particular ADCs formed by the selective reduction of the capped antibodies' cysteine residues, and ADCs formed using chemical handles such as aldehyde/azide/alkyne biorthogonal groups, which permit additional drug conjugation chemistry; and uncapped antibodies produced by cells in low cysteine, cysteine and glutathione media, and ADCs produced via direct conjugation to these uncapped antibodies.

Capped and uncapped antibody cysteines, and their use in antibody-drug conjugation

This invention relates to methods for rationally designing cell culture media for use in cell cultures, e.g., cell cultures employed in polypeptide production; cell culture media designed with the disclosed methods; methods of producing a polypeptide of interest, e.g., an antibody, using such media; polypeptides produced using the methods and media disclosed herein; and pharmaceuticals compositions containing such polypeptides. The rationally designed media contain a concentration of an amino acid that is calculated for use in cell mass, a concentration of the amino acid that is calculated for use in cell maintenance, and a concentration of the amino acid that is calculated for incorporation into the polypeptide of interest.

Rationally designed media for cell culture

An improved system for large scale production of proteins and/or polypeptides in cell culture is provided. In accordance with the present invention, cells expressing the protein or polypeptide of interest are grown in media that comprise a glycolysis-inhibiting substance. Additionally and/or alternatively, cells expressing the protein or polypeptide of interest are grown in media in which glutamine is limited. The use of such a system allows high levels of protein or polypeptide production and lessens accumulation of undesirable metabolic waste products such as lactate. Proteins and polypeptides expressed in accordance with the present invention may be advantageously used in the preparation of pharmaceutical, immunogenic, agricultural or other commercial compositions.

Glycolysis-inhibiting substances in cell culture

Methods and processes for improved recombinant protein production are provided. The methods are useful for production of growth factors, particularly those of the TGF-&#x3b2; superfamily, including bone morphogenetic proteins (BMPs), such as BMP-2. Suitable host cells are cultured in media where iron is present at a concentration of at least 2.25 &#x3bc;M and if pyridoxal is present, it makes up less than 55% of the molar concentration of vitamin B6 in the media.

Methods for enhanced production of bone morphogenetic proteins

An improved system for large scale production of proteins and/or polypeptides in cell culture, particularly in media characterized by one or more of: i) a cumulative amino acid concentration greater than about 70 mM; ii) a molar cumulative glutamine to cumulative asparagine ratio of less than about 2; iii) a molar cumulative glutamine to cumulative total amino acid ratio of less than about 0.2; iv) a molar cumulative inorganic ion to cumulative total amino acid ratio between about 0.4 to 1; or v) a combined cumulative glutamine and cumulative asparagine concentration between about 16 and 36 mM, is provided. The use of such a system allows high levels of protein production and lessens accumulation of certain undesirable factors such as ammonium and/or lactate. Additionally, culture methods including a temperature shift, typically including a decrease in temperature when the culture has reached about 20-80% of it maximal cell density, are provided. Alternatively or additionally, the present invention provides methods such that, after reaching a peak, lactate and/or ammonium levels in the culture decrease over time.

Production of anti-abeta

Production of TNFR-Ig

Production of polypeptides

Growing community of inventors

North Chelmsford, MA, United States of America

Wenge Wang