公开(公告)号：US11198736B2

公开(公告)日：2021-12-14

申请号：US16707940

申请日：2019-12-09

申请人： ImmunoGen, Inc.

发明人： Olga Ab ,  Daniel Tavares ,  Juliantro Setiady ,  Sharron Ladd ,  Christina N. Carrigan ,  Lingyun Rui

IPC分类号： C07K16/30 ,  C07K16/28 ,  A61K47/68 ,  A61K39/00 ,  G01N33/574 ,  G01N33/547

摘要： The invention generally relates to antibodies that bind to human folate receptor and diagnostic assays for folate receptor 1-based therapies. Methods of using the antibodies to monitor therapy are further provided.

公开(公告)号：US20210230114A1

公开(公告)日：2021-07-29

申请号：US17143723

申请日：2021-01-07

申请人： IMMUNOGEN, INC.

发明人： Michael Reardon ,  Richard A. Silva

IPC分类号： C07D207/448 ,  C07D519/00

摘要： The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

公开(公告)号：US20210171546A1

公开(公告)日：2021-06-10

申请号：US16991700

申请日：2020-08-12

申请人： IMMUNOGEN, INC.

发明人： Baudouin Gérard ,  Manami Shizuka ,  Michael Louis Miller ,  Richard A. Silva

IPC分类号： C07D519/00 ,  C07K5/083 ,  C07D487/04

摘要： The invention relates to novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

公开(公告)号：US20210101871A1

公开(公告)日：2021-04-08

申请号：US17023545

申请日：2020-09-17

申请人： IMMUNOGEN, INC.

发明人： Scott A. Hilderbrand ,  Benjamin M. Hutchins

IPC分类号： C07D243/26 ,  C07D487/04 ,  C07K16/28 ,  A61K47/68

摘要： The invention relates to novel methods of preparing cell-binding agent-cytotoxic agent conjugates, wherein the cytotoxic agent is an imine-containing cytotoxic agent bearing a maleimide group. In some embodiments, the cell-binding agent (CBA) is covalently linked to the cytotoxic agent through an engineered Cys, such as an engineered Cys in the heavy chain CH3 domain, at a position corresponds to the EU/OU numbering position 442 (or C442) on an antibody CBA. The invention also provides conjugates prepared by the methods of the present invention, compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the conjugates of the invention.

公开(公告)号：US10968228B2

公开(公告)日：2021-04-06

申请号：US16560379

申请日：2019-09-04

申请人： IMMUNOGEN, INC.

发明人： Baudouin Gérard ,  Richard A. Silva ,  Michael Louis Miller ,  Manami Shizuka

IPC分类号： C07D487/22 ,  C07D487/04 ,  C07D209/12

摘要： The invention provides novel methods for preparing indolinobenzodiazepine monomer compounds of formula (I) below and their synthetic precursors:

公开(公告)号：US10947315B2

公开(公告)日：2021-03-16

申请号：US16229028

申请日：2018-12-21

申请人： IMMUNOGEN, INC.

发明人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V. J. Chari

IPC分类号： C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  A61K47/60 ,  A61P35/00 ,  C07K16/28 ,  A61K47/68 ,  A61K45/06 ,  A61K31/5517 ,  A61K38/07 ,  C07K5/103 ,  C07K5/02 ,  C07K16/46 ,  C07K19/00

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

公开(公告)号：US10944190B2

公开(公告)日：2021-03-09

申请号：US16574718

申请日：2019-09-18

申请人： IMMUNOGEN, INC.

发明人： Wayne C. Widdison ,  Robert Yongxin Zhao

IPC分类号： C07D498/16 ,  C07D498/18 ,  H01R12/58 ,  H05K1/02 ,  H05K1/11 ,  H05K1/18

摘要： Disclosed is a method of preparing an amino acid ester of maytansinol by reacting maytansinol with an N-carboxyanhydride of an amino acid (NCA) in the presence of a drying agent. Also disclosed is an improved method of preparing an amino acid ester of maytansinol in which a nucleophile is added to the reaction mixture after completion of the reaction between maytansinol and an N-carboxyanhydride of an amino acid.

公开(公告)号：US10913713B2

公开(公告)日：2021-02-09

申请号：US16679593

申请日：2019-11-11

申请人： IMMUNOGEN, INC.

发明人： Michael Reardon ,  Richard A. Silva

IPC分类号： C07D207/452 ,  C07D487/04 ,  C07D207/448 ,  C07D519/00

摘要： The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

公开(公告)号：US20200046634A1

公开(公告)日：2020-02-13

申请号：US16389396

申请日：2019-04-19

申请人： ImmunoGen, Inc.

发明人： Kelli RUNNING ,  Robert A. MASTICO ,  James J. O'LEARY ,  Olga AB ,  Beni WOLF

IPC分类号： A61K9/00 ,  A61K45/06 ,  A61K31/5365 ,  C07K16/28 ,  A61K31/573 ,  A61K47/68

摘要： Methods of administering immunoconjugates that bind to FOLR1 are provided. The methods comprise administering an anti-FOLR1 immunoconjugate to a person in need thereof, for example, a cancer patient, at a therapeutically effective dosing regimen that results in minimal adverse effects.

公开(公告)号：US10370389B2

公开(公告)日：2019-08-06

申请号：US15837832

申请日：2017-12-11

申请人： IMMUNOGEN, INC.

发明人： Baudouin Gérard ,  Manami Shizuka ,  Michael Louis Miller ,  Richard A. Silva

IPC分类号： C07D519/00 ,  C07D487/04 ,  C07K5/083

摘要： The invention relates to novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.