Single Chain Antibody Medications for(+)METH Abuse

描述（由申请人提供）： 本研究的目的是开发抗药物单链抗体（scFv）作为治疗药物滥用的潜在药物。这些单链抗体将源自目前可用的抗（+）甲基苯丙胺单克隆抗体（mAb）的可变区结构域。然而，它们将被重新工程化以具有优于亲本mAb的免疫学、药代动力学和亲和力优势。在第一个具体目标中，scFv将通过用多肽接头连接原型mAb的重链和轻链可变区来重组工程化以产生单基因产物。该产品将在细菌系统中生产，这可能导致更便宜的蛋白质药物。在第二个目标中，然后将使用体外进化技术来产生具有新序列的scFv，然后选择新序列以提高亲和力和特异性。在第三个目标中，用聚（乙二醇）对scFv进行化学修饰将用于开发具有改善的药代动力学特性的药物。可以预见，具有定制的亲和力和药代动力学性质的工程抗体片段将是治疗甲基苯丙胺滥用的重要创新。

DESCRIPTION (provided by applicant): The goal of this research is to develop anti-drug single chain antibodies (scFv) as potential medications for treating drug abuse. These scFv will be derived from the variable region domains of currently available anti- (+)methamphetamine monoclonal antibodies (mAb). However, they will be reengineered to possess immunological, pharmacokinetic, and affinity advantages over the parent mAb. In the first specific aim, the scFv will be recombinantly engineered by connecting the heavy and light chain variable regions of the prototype mAb with a polypeptide linker to create a single gene product. This product will be produced in bacterial systems, which could lead to less expensive protein medications. In the second aim, in vitrc evolution techniques will then be used to generate scFv with new sequences that are then selected for improved affinity and specificity. In a third aim, chemical modifications of scFv with poly(ethylene glycol) will be used to develop medications with improved pharmacokinetic properties. It is envisioned that an engineered antibody fragment with customized affinity and pharmacokinetic properties will be an important innovation for the treatment of methamphetamine abuse.