David M. Goldenberg,Chien-Hsing Chang,Hans J. Hansen
申请号：
US13617059
公开号：
US20130078182A1
申请日:
2012.09.14
申请国别(地区):
US
年份:
2013
代理人:
摘要：
Substituted humanized, chimeric or human anti-CD20 antibodies or antigen binding fragments and bispecific antibodies or fusion proteins comprising the substituted antibodies or antigen binding fragments are disclosed. They are useful for treatment of B-cell disorders, such as B-cell malignancies and autoimmune diseases, as well as GVHD, organ transplant rejection, and hemolytic anemia and cryoglobulinemia. Substitution of an aspartate residue at Kabat position 101 of CDR3 VH (CDRH3), produces improved therapeutic properties, including decreased dissociation rates and improved CDC activity, apoptosis, B-cell depletion and therapeutic efficacy at very low dosages. Veltuzumab, a humanized antibody that incorporates such sequence variation, exhibits improved therapeutic efficacy compared to similar antibodies of different CDRH3 sequence, allowing therapeutic effect at dosages as low as 200 mg or less, preferably 100 mg or less, preferably 80 mg or less, preferably 50 mg or less, most preferably 30 mg or less of naked antibody administered i.v. or s.c.
