BARAT, BHASWATI,巴拉特 巴斯娃缇,巴拉特 巴斯娃緹,JOHNSON, LESLIE S.,强生 莱斯利,強生 萊斯利,MOORE, PAUL A.,摩尔 保罗,摩爾 保羅,ALDERSON, RALPH FROMAN,安德森瑞夫 佛曼,安德森瑞夫 佛曼,BONVINI, EZIO,波维尼 爱利欧,波維尼 愛利歐
申请号：
TW106104961
公开号：
TW201730212A
申请日:
2017.02.15
申请国别(地区):
TW
年份:
2017
代理人:
摘要：
The present invention is directed to optimized ROR1-binding molecules having enhanced affinity and superior ability to mediate redirected cytotoxicity of tumor cells relative to prior ROR1-binding molecules. More specifically, the invention relates to optimized ROR1-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been optimized for binding to an epitope present on the human ROR1 polypeptide so as to exhibit enhanced binding affinity for human ROR1 and/or a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific ROR1-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such optimized ROR1-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such ROR1-binding molecules, and to methods involving the use of any of such ROR1-binding molecules in the treatment of cancer and other diseases and conditions.本發明涉及優化的ROR1-結合分子,其相對於現有的ROR1-結合分子具有增強的親和力和介導對腫瘤細胞的重定向細胞毒性的更好的能力。更具體地,本發明涉及包括可變輕鏈和/或可變重鏈(VH)結構域的優化的ROR1-結合分子,所述可變輕鏈和/或可變重鏈(VH)結構域已經被優化以結合存在於人ROR1多肽上的表位元,以便顯示出對人ROR1增強的結合親和力和/或在施用於接受受試者後降低的免疫原性。本發明特別涉及雙特異性,三特異性或多特異性ROR1-結合分子,包括雙特異性雙抗體、BiTEs、雙特異性抗體、三價結合分子等,其包括:(i)這樣的優化的結合 ROR1的可變結構域和(ii)能夠結合存在於效應細胞表面上的分子的表位元的結構域。本發明還涉及包含任何這樣的ROR1-結合分子的藥物組合物,以及涉及包括在癌症和其它疾病和狀況的治療中使用任何這樣的ROR1-結合分子的方法。
