公开(公告)号：US20230075422A1

公开(公告)日：2023-03-09

申请号：US17787461

申请日：2020-12-18

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Ping XU ,  Anurag Khetan ,  Rodney Lawrence Parsons ,  Michael J. Smith ,  Michael Anthony Schmidt

IPC: C07K16/00 ,  C12N5/07 ,  A61P35/00

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.