发明名称 |
Single domain brain-targeting antibody fragments derived from llama antibodies |
摘要 |
A phage-displayed library of llama single heavy domain antibodies (sdAbs) was enriched for species that selectively bind to and are internalized by human cerebromicrovascular endothelial cells (HCEC). From the enriched library, two sdAbs were selected, sequenced, subcloned, and expressed as fusion proteins with c-myc-His5 tags (His5 is SEQ ID NO:101). Similarly as phage-displayed sdAbs, these soluble tagged sdAbs were shown to selectively bind to HCEC and to transmigrate across in vitro human blood-brain barrier (BBB) model. In contrast to an unrelated llama sdAb, these sdAbs were also detected in the brain after i.v. injection into mice. These small (˜13 kDa) antibody fragments have essential characteristics of brain-specific delivery vectors and can be used to facilitate drug transport across the BBB. |
申请公布号 |
US8715659(B2) |
申请公布日期 |
2014.05.06 |
申请号 |
US201313773734 |
申请日期 |
2013.02.22 |
申请人 |
NATIONAL RESEARH COUNCIL OF CANADA;NATIONAL RESEARCH COUNCIL OF CANADA |
发明人 |
MURUGANANDAM ARUMUGAM;TANHA JAMSHID;NARANG SARAN;STANIMIROVIC DANICA |
分类号 |
A61K39/395;A61K39/00;A61K39/38;C07K14/00;C07K16/00;C07K16/28;C07K17/00;C12N15/10;C40B40/02 |
主分类号 |
A61K39/395 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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