公开(公告)号：US20200253768A1

公开(公告)日：2020-08-13

申请号：US16850920

申请日：2020-04-16

Applicant: NOVARTIS AG

Inventor： Qi-Ying HU ,  Hidetomo IMASE

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

Abstract: 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：US20190038444A1

公开(公告)日：2019-02-07

申请号：US16035241

申请日：2018-07-13

Applicant: NOVARTIS AG

Inventor： Qi-Ying HU ,  Hidetomo IMASE

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

Abstract: 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：US20220363671A1

公开(公告)日：2022-11-17

申请号：US17642292

申请日：2020-09-16

Applicant: NOVARTIS AG

Inventor： Jake AXFORD ,  Rohan Eric John BECKWITH ,  Simone BONAZZI ,  Nicole BUSCHMANN ,  Artiom CERNIJENKO ,  Janetta DEWHURST ,  Aleem FAZAL ,  Matthew James HESSE ,  Lauren HOLDER ,  Viktor HORNAK ,  Hidetomo IMASE ,  Rama JAIN ,  Xianming JIN ,  John Ryan KERRIGAN ,  Julie LACHAL ,  Fupeng MA ,  Hasnain Ahmed MALIK ,  James R. MANNING ,  Daniel MCKAY ,  Robert Joseph MOREAU ,  Pierre NIMSGERN ,  Gary O'BRIEN ,  Anna VULPETTI ,  Ken YAMADA ,  Junping ZHAO

IPC: C07D405/04 ,  A61K31/513 ,  C07D471/04 ,  C07D413/04 ,  C07D401/14

Abstract: Described herein are glue degrader compounds, their various targets, their preparation, pharmaceutical compositions comprising them, and their use in the treatment or prevention of conditions, diseases, and disorders mediated by various target proteins.