公开(公告)号：EP3655395A2

公开(公告)日：2020-05-27

申请号：EP18785785.9

申请日：2018-07-19

申请人： Bristol-Myers Squibb Company

发明人： AYTAR, Burcu Selin ,  BOROVIKA, Alina ,  CHAN, Collin ,  DEERBERG, Joerg ,  DOMAGALSKI, Nathan R. ,  EASTGATE, Martin D. ,  FAN, Yu ,  FENSTER, Michael David Bengt ,  FOREST, Robert V. ,  GONZALEZ-BOBES, Francisco ,  GREEN, Rebecca A. ,  HICKEY, Matthew R. ,  KOPP, Nathaniel David ,  LA CRUZ, Thomas E. ,  LAUSER, Kathleen ,  LEE, Hong Geun ,  LEAHY, David K. ,  LUO, Helen Y. ,  RAZLER, Thomas M. ,  SAVAGE, Scott A. ,  SFOUGGATAKIS, Chris ,  SOUMEILLANT, Maxime C.D. ,  ZARETSKY, Serge ,  ZHENG, Bin ,  ZHU, Ye

IPC分类号： C07D235/06 ,  C07C233/41 ,  C07D487/04 ,  C07D207/273

公开(公告)号：EP3380487B1

公开(公告)日：2020-09-02

申请号：EP16816042.2

申请日：2016-11-22

申请人： Bristol-Myers Squibb Company

发明人： HICKEY, Matthew R. ,  RAMIREZ, Antonio

IPC分类号： C07K1/107 ,  A61K47/60 ,  C07K14/50 ,  C07K14/64

公开(公告)号：EP3789395A1

公开(公告)日：2021-03-10

申请号：EP20189107.4

申请日：2016-11-22

申请人： Bristol-Myers Squibb Company

发明人： HICKEY, Matthew R. ,  RAMIREZ, Antonio

IPC分类号： C07K1/107 ,  A61K47/60 ,  C07K14/50 ,  C07K14/64

摘要： The present disclosure provides an additive system for use in protein PEGylation. The additive system includes />aminobenzoic hydrazide used either alone or in combination with aromatic amines, such as 3,5-diaminobenzoic acid, or with ammonium sals such as ammonium chloride or ammonium acetate. The disclosed additive combination provides several benefits including increased reaction rates, higher yields and reduction in the aminoxy-PEG equivalents required to complete the conjugation reaction. Typical reactions can be run by combining the additive or additive system with a solution of a protein and aminoxy-PEG reagent. The solution is adjusted to pH 4 and held at 20-25 °C without stirring until completion, typically within 24 hours.

公开(公告)号：EP3380487A1

公开(公告)日：2018-10-03

申请号：EP16816042.2

申请日：2016-11-22

申请人： Bristol-Myers Squibb Company

发明人： HICKEY, Matthew R. ,  RAMIREZ, Antonio

IPC分类号： C07K1/107 ,  A61K47/60 ,  C07K14/50 ,  C07K14/64

摘要： The present disclosure provides an additive system for use in protein PEGylation. The additive system includes p-aminobenzoic hydrazide used either alone or in combination with aromatic amines, such as 3,5-diaminobenzoic acid, or with ammonium salts such as ammonium chloride or ammonium acetate. The disclosed additive combination provides several benefits including increased reaction rates, higher yields and reduction in the aminoxy-PEG equivalents required to complete the conjugation reaction. Typical reactions can be run by combining the additive or additive system with a solution of a protein and aminoxy-PEG reagent. The solution is adjusted to pH 4 and held at 20-25° C. without stirring until completion, typically within 24 hours.