Anurag Khetan - Lexington MA, US Yao-ming Huang - San Diego CA, US Jana Dolnikova - Waltham MA, US Nels Pederson - Mansfield MA, US Helena Yusuf-Makagiansar - San Diego CA, US Paul Chen - Belmont MA, US Thomas Ryll - Lexington MA, US
The present invention relates to methods of reducing substitution of amino acids during the production of polypeptides of interest in mammalian cells. By varying the concentration of amino acids in the culture medium, heterogeneity of the polypeptide's amino acid sequence is decreased, leading to higher yields of functional protein.
Use Of Fucosylation Inhibitor For Producing Afucosylated Antibody
- Princeton, US Anurag Khetan - Princeton NJ, US Rodney Lawrence Parsons - Yardley PA, US Michael J. Smith - Somerset NJ, US Michael Anthony Schmidt - Cranbury NJ, US
International Classification:
C07K 16/00 C12N 5/07 A61P 35/00
Abstract:
The present invention provides inhibitors of fucosylation during protein expression from mammalian cells. The inhibitors are derived from rhamnose and act by inhibition of GDP-mannose 4,6-dehydratase (GMD). The invention further provides methods of making proteins with reduced level of fucosylation, such as antibodies and antibodies made by the methods of the present invention. Such hypofucosylated or nonfucosylated antibodies may find use, for example, in treatment of human disease in which is it therapeutically eneficial to direct antibody dependent cellular cytotoxicity (ADCC) mediated killing of cells expressing the antibody target on their surface, for example in depletion of Tregs in cancer patients using a hypofucosylated or nonfucosylated anti-CTLA-4 antibody.