GOLDENBERG, DAVID M.,CHANG, CHIEN-HSING,HANSEN, HANS J.
申请号：
CA2731255
公开号：
CA2731255C
申请日:
2009.07.21
申请国别(地区):
CA
年份:
2018
代理人:
摘要：
The present invention provides substituted humanized, chimeric or human anti-CD20 antibodies or antigen bindingfragments thereof and bispecific antibodies or fusion proteins comprising thesubstituted antibodies or antigen binding fragmentsthereof. The antibodies, fusion proteins or fragments are useful for treatmentof B-cell disorders, such as B-cell malignanciesand autoimmune diseases, as well as GVHD, organ transplant rejection, andhemolytic anemia and cryoglobulinemia. Aminoacid substitutions, particularly substitution of an aspartate residue at Kabatposition 101 of CDR3 V H (CDRH3), result in improvedtherapeutic properties, such as decreased dissociation rates, improved CDCactivity, improved apoptosis, improved B-celldepletion and improved therapeutic efficacy at very low dosages. Veltuzumab, ahumanized anti-CD20 antibody that incorporatessuch sequence variations, exhibits improved therapeutic efficacy compared tosimilar antibodies of different CDRH3 sequence, allowingtherapeutic effect at dosages as low as 200 mg or less, more preferably 100 mgor less, more preferably 80 mg or less,more preferably 50 mg or less, most preferably 30 mg or less of naked antibodywhen administered i.v. or s.c.
