SINGH, SANJAYA,辛格 山加亚,辛格 山加亞,FUNG, MICHAEL S. C.,方 麦可Ｓ Ｃ,方 麥可Ｓ Ｃ,HUANG, DAN,黄丹阳,黃丹陽,辛格 山加亚,辛格 山加亞,方 麦可S C,方 麥可S C
申请号：
TW103100837
公开号：
TW201439119A
申请日:
2008.04.28
申请国别(地区):
TW
年份:
2014
代理人:
摘要：
Novel antibodies and their fragments are disclosed that specifically bind to CD4. Anti-CD4 antibodies are disclosed having amino acid substitutions in the hinge region that prevent intrachain disulfide bond formation resulting in antibody molecules with surprisingly improved bivalent stability. Increased stability facilitates manufacturing and provides increased in vivo stability. Antibodies are also disclosed that have amino acid substitutions that reduce binding to Fc receptor and ADCC activity that also result in a surprising effect on CD4 internalization. In addition, genes for such antibodies are disclosed that have been modified such that they have increased expression over their unmodified counterparts.本發明揭示與CD4特異性結合之新穎抗體及其片段。本發明揭示抗-CD4抗體，其在鉸鏈區中具有防止鏈內雙硫鍵形成之胺基酸取代，造成具有令人驚訝之改良二價穩定性之抗體分子。增加之穩定性有利於製造，且提供增加之活體內穩定性。本發明亦揭示具有減少與Fc受體結合及ADCC活性且對CD4內化亦產生令人驚訝效應之胺基酸取代的抗體。另外，本發明揭示該等抗體之基因，該等基因已經修飾以使其具有增加之表現超過其未經修飾對應物。
