Wyeth

Pfizer Corporation

Jose Manuel Gomes

Gregory Walter Hiller

Yen-Tung Luan

Wenge Wang

Denis Drapeau

Xiaotian Zhong

Amarnauth Shastrie Prashad

Terry Cardoza

Kaushik Dutta

Frank W Kotch

Vimalkumar B Patel

Renee L Procopio-melino

Gregg Nyberg

Renee L Procopio-Melino

Optimizing production of selectively capped, and uncapped, cysteines on antibodies by manipulation of cell growth conditions including the deliberate depletion of cysteine and/or cystine in the cell culture process by way of media components, batch duration, or cell density to achieve efficient production of proteins including antibody-drug-conjugates (ADCs).; conjugating a TNB-capped cysteine-containing protein by reacting it with a reducing agent capable of detaching the TNB-capping moieties from the protein without significantly reducing antibody inter-chain sulfur bonds, and conjugating reduced sulfur bonds on the protein to a payload through a reactive linking moiety.

Large scale production process for capped and un-capped antibody cysteines and their use in therapeutic protein conjugation

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

The present disclosure provides a method of reducing protein misfolding and aggregation in the cell culture by growing the cell culture at a reduced temperature and/or reduced pH. As a result, the quality of the protein produced in the cell culture is greatly improved. Thus, the present disclosure facilitates improvements in the efficacy of therapeutic proteins produced in cell culture.

Use of low temperature and/or low pH 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

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Chelmsford, MA, United States of America

Jose Manuel Gomes