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.

公开(公告)号：US20240182456A1

公开(公告)日：2024-06-06

申请号：US18554778

申请日：2022-04-11

申请人： Novartis AG

发明人： Martin ALLAN ,  Matthew CARSON ,  Thomas CAYA ,  Lara CZABANIUK ,  Ming QIAN ,  Daniel SMITH ,  Troy SMITH ,  Liansheng SU ,  Chung-Yeh WU ,  Lihua YANG ,  Chun ZHANG ,  Ping ZHANG ,  Xilin ZHOU

IPC分类号： C07D405/14 ,  C07D413/14 ,  C07D417/14

CPC分类号： C07D405/14 ,  C07D413/14 ,  C07D417/14

摘要： The present invention relates to compounds of formula (I) as activators of glucagon-like peptide 1 (GLP1) receptor for the treatment of obesity, type 2 diabetes mellitus, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, one or more diabetic complications, diabetic nephropathy, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hypertension, atherosclerosis, peripheral arterial disease, stroke, cardiomyopathy, atrial fibrillation, heart failure, coronary heart disease and neuropathy. Preferred compounds are e.g. 2-((4-((S)-2-(4-chloro-2-fluorophenyl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-imidazole derivatives and similar compounds, such as e.g. C-1, C-2, C-3, C-4 and other compounds.

公开(公告)号：US20240309084A1

公开(公告)日：2024-09-19

申请号：US18272702

申请日：2022-01-18

申请人： Novartis AG

发明人： Martin ALLAN ,  Jeffrey BAGDANOFF ,  David Weninger BARNES ,  John BLANKENSHIP ,  James BRADNER ,  Kevin CLAIRMONT ,  Brian GRANDA ,  Guido JUNGE ,  Thomas SMITH ,  Elisabetta TRAGGIAI ,  Max WARNCKE

IPC分类号： C07K16/28 ,  A61K47/54 ,  A61K47/68 ,  C07K16/40

CPC分类号： C07K16/28 ,  A61K47/549 ,  A61K47/6849 ,  C07K16/40 ,  C07K2317/31 ,  C07K2317/62 ,  C07K2317/70

摘要： The present disclosure features bifunctional compounds for the degradation of extracellular targets, as well as compositions and related methods thereof.

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.