31-12-2020 дата публикации
Номер: US20200407440A1
Принадлежит:
Amatoxins, as well as antibody-drug conjugates (ADCs) comprising an amatoxin are provided, as well as compositions and methods of using the same. The compositions and methods provided herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure. Methods and compositions for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, as well as prevention of graft-versus-host-disease (GVHD), are provided. 4. The ADC of wherein L comprises one or more of a bond claim 1 , —(C═O)— claim 1 , a —C(O)NH— group claim 1 , an —OC(O)NH— group claim 1 , C-Calkylene claim 1 , C-Cheteroalkylene claim 1 , C-Calkenylene claim 1 , C-Cheteroalkenylene claim 1 , C-Calkynylene claim 1 , C-Cheteroalkynylene claim 1 , C-Ccycloalkylene claim 1 , heterocycloalkylene claim 1 , arylene claim 1 , heteroarylene claim 1 , a —(CHCHO)— group where p is an integer from 1-6 claim 1 , or a solubility enhancing group;{'sub': 1', '6', '1', '6', '2', '6', '2', '6', '2', '6', '2', '6', '3', '6, 'wherein each C-Calkylene, C-Cheteroalkylene, C-Calkenylene, C-Cheteroalkenylene, C-Calkynylene, C-Cheteroalkynylene, C-Ccycloalkylene, heterocycloalkylene, arylene, or heteroarylene may optionally be substituted with from 1 to 5 substituents independently selected for each occasion from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, alkaryl, alkyl heteroaryl, amino, ammonium, acyl, acyloxy, acylamino, aminocarbonyl, alkoxycarbonyl, ureido, carbamate, aryl, heteroaryl, sulfinyl, sulfonyl, hydroxyl, alkoxy, sulfanyl, halogen, carboxy, trihalomethyl, cyano, hydroxy, mercapto, and nitro;'}{'sub': 1', '6', '1', '6', '2', '6', '2', '6', '2', '6', '2', '6', '3', '6, 'or each C-Calkylene, C-Cheteroalkylene, C-Calkenylene, C-Cheteroalkenylene, C- ...
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