| abstract |
The present invention provides humanized, chimeric or human, substituted anti-CD2O antibodies or their antigen-binding fragments and bispecific antibodies or fusion proteins comprising the substituted antibodies or their antigen-binding fragments. Antibodies, fusion proteins or fragments are useful for the treatment of B cell disorders, such as B cell malignancy and autoimmune diseases, as well as GVHD, organ transplant rejection and hemolytic anemia and cryoglobulinemia. Amino acid substitutions, particularly the substitution of an aspartate residue at Kabat position 101 of VH of CDR3 (CDRH3), results in improved therapeutic properties, such as decreased dissociation regimens, enhanced CDC activity, enhanced apoptosis, weakening of B cell and improved therapeutic efficacy at very low dosages. Veltuzumab, a humanized anti-CD20 antibody that incorporates such sequence variations, exhibits improved therapeutic efficacy compared to similar antibodies of different CDRH3 sequence, which allows the therapeutic effect at dosages as low as 200 mg or less, more preferably 100 mg or less, more preferably 80 mg or less, most preferably 30 mg or less of naked antibody when i is administered. v. or s. C. |