A general approach to sitespecific antibody （特定抗体的一般方法）.pdf

A general approach to site-specific antibody drug conjugates a,1 a a a a,2 a a Feng Tian , Yingchun Lu , Anthony Manibusan , Aaron Sellers , Hon Tran , Ying Sun , Trung Phuong , Richard Barnetta a a b b,3 c , Brad Hehli , Frank Song , Michael J. DeGuzman , Semsi Ensari , Jason K. Pinkstaff , Lorraine M. Sullivanc c d e,1 f f f , Sandra L. Biroc , Ho Cho , Peter G. Schultz , John DiJoseph , Maureen Dougher , Dangshe Ma , Russell Dushing h i i,4 f f,1 , Mauricio Leal , Lioudmila Tchistiakova , Eric Feyfant , Hans-Peter Gerber , and Puja Sapra aEuCode Technology, Ambrx, Inc., La Jolla, CA 92037; bCMC Department and cPreclinical Science, dAmbrx, Inc., La Jolla, CA 92037; eDepartment of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037; fOncology Research Unit and hPharmacokinetics, Dynamics and Metabolism, Pfizer, Inc., Pearl River, NY 10965; gWorldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340; and iGlobal BioTherapeutic Technologies, Pfizer, Inc., Cambridge, MA 02140 Contributed by Peter G. Schultz, December 10, 2013 (sent for review October 1, 2013) Using an expanded genetic code, antibodies with site-specifically potency, improved PK, and an expanded therapeutic window (6, 7). incorporated nonnative amino acids were prod