公开(公告)号：US20200253768A1

公开(公告)日：2020-08-13

申请号：US16850920

申请日：2020-04-16

申请人： NOVARTIS AG

发明人： Qi-Ying HU ,  Hidetomo IMASE

IPC分类号： A61F5/00 ,  A61K47/68 ,  A61F5/56 ,  A61C5/90 ,  A61K47/64 ,  A61K47/54

摘要： The invention provides methods to prepare protein conjugates from proteins having at least two cysteines. In one embodiment, a protein with a disulfide linkage is reduced to provide two free cysteines for reaction with a 1,3-dihaloacetone or similar reactant, linking the sulfur atoms of the two cysteines together. The ketone inserted between the sulfur atoms is then used to form a Schiff base to an aminated payload molecule, thus conjugating the protein to a payload. In another embodiment, two cysteine residues are tied together by reaction with a 1,3-dihaloacetone or similar reactant. The linkage between the sulfur atoms in each case holds the protein or peptide in a constrained conformation, while also providing a convenient place for attaching a payload with good specificity and efficiency.

公开(公告)号：US20190381126A1

公开(公告)日：2019-12-19

申请号：US16524951

申请日：2019-07-29

申请人： NOVARTIS AG

发明人： Qi-Ying HU ,  Martin ALLAN

IPC分类号： A61K38/05 ,  A61K47/68

摘要： The invention provides methods to prepare protein conjugates from proteins having at least four accessible cysteine residues. In one embodiment, an antibody with four reducible disulfide linkages is reduced to provide four pairs of free cysteines. Each pair of free cysteines is reacted with a 1,3-dihaloacetone or similar reactant, linking the sulfur atoms of each pair together though a 3-carbon tether with a reactive ketone. A pair of these reactive ketones are linked together with and used to attach a single payload molecule, thus conjugating the antibody to two payload groups. This method gives a stabilized antibody conjugate with high selectivity for a ratio of two payloads per antibody.

公开(公告)号：US20190038444A1

公开(公告)日：2019-02-07

申请号：US16035241

申请日：2018-07-13

申请人： NOVARTIS AG

发明人： Qi-Ying HU ,  Hidetomo IMASE

IPC分类号： A61F5/00 ,  A61K47/68 ,  A61F5/56 ,  A61C5/90 ,  A61K47/54 ,  A61K47/64

摘要： The invention provides methods to prepare protein conjugates from proteins having at least two cysteines. In one embodiment, a protein with a disulfide linkage is reduced to provide two free cysteines for reaction with a 1,3-dihaloacetone or similar reactant, linking the sulfur atoms of the two cysteines together. The ketone inserted between the sulfur atoms is then used to form a Schiff base to an aminated payload molecule, thus conjugating the protein to a payload. In another embodiment, two cysteine residues are tied together by reaction with a 1,3-dihaloacetone or similar reactant. The linkage between the sulfur atoms in each case holds the protein or peptide in a constrained conformation, while also providing a convenient place for attaching a payload with good specificity and efficiency.

公开(公告)号：US20170095572A1

公开(公告)日：2017-04-06

申请号：US15312267

申请日：2015-05-22

申请人： NOVARTIS AG

发明人： Qi-Ying HU ,  Martin ALLAN

IPC分类号： A61K39/00 ,  A61K38/05

CPC分类号： A61K38/05 ,  A61K47/68 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6855

摘要： The invention provides methods to prepare protein conjugates from proteins having at least four accessible cysteine residues. In one embodiment, an antibody with four reducible disulfide linkages is reduced to provide four pairs of free cysteines. Each pair of free cysteines is reacted with a 1,3-dihaloacetone or similar reactant, linking the sulfur atoms of each pair together though a 3-carbon tether with a reactive ketone. A pair of these reactive ketones are linked together with and used to attach a single payload molecule, thus conjugating the antibody to two payload groups. This method gives a stabilized antibody conjugate with high selectivity for a ratio of two payloads per antibody.