第四章 抗体制药专题.ppt

第四章 抗体制药专题;第一节 抗体结构与治疗作用 抗体结构;;;抗体的治疗作用;分类;第二节 单克隆抗体;简单生产过程;单克隆抗体的不足;第三节 人源化单克隆抗体;人源化单克隆抗体技术前景;抗体的人源化主要应考虑到两个基本的原则： ;目前报道的人源化方法主要有:;嵌合抗体;嵌合抗体的产品实例;嵌合抗体;表面重塑;重构抗体;抗体功能片段;;第三节 抗体库与基因工程抗体技术;噬菌体抗体库技术: ;构建方法:;抗体库筛选;;;;;;;The Display CycleThe display process used by Discerna is remarkably robust and can be summarised in the following sequence of seven technically simple steps:1. Take genes encoding the protein.2. Amplify genes using standard methods.3. Produce proteins tagged with their encoding gene in vitro.4. Affinity purify proteins using an appropriate ligand or antigen.5. Amplify the genes encoding the purified proteins using standard methods.6. Clone genes and express in bacteria.7. Lyse bacteria and purify proteins for use.;DiscernArray? DiscernArray? technology is a combination of PCR and cell free synthesis which allows the high speed parallel synthesis of antobodies. The final stages of the process can allow an array of antibodies to be produced. In principal the technology can be applied to any type of protein.;;Features1. DiscernArray? converts PCR DNA into an antobody array in 3 hours or less, with no cloning or additional protein purification. 2. DiscernArray? replace cloning, in vivo expression systems and purification procedures, avoiding inclusion bodies, aggregation or degradation associated with bacterial expression. 3. DiscernArray? can be made in high throughput format by carrying out multiple transcription/translation reactions in parallel.;;如何生产基因工程抗体？;;;转基因组鼠生产人类抗体？;;第四节 抗体治疗;;抗体免疫偶联物（Immunocojugates）;;重组免疫毒素;抗体靶向的酶前药治疗;;;简单介绍;;制备;;催化抗体的筛选; ;纯化学筛选法 荧光标记筛选法 化学直接筛选法 纯化学的筛选只能筛选出与Hapten高结合性的抗体酶，但是这种结合却与抗体酶的高催化活性不存在直接的关系。;存在的问题;可能的应用;在戒毒方面的应用 难题： 毒品一直困扰着人类，很多人在吸毒上瘾或很难戒掉， 1）直接拮抗可卡因上瘾的抗体至今还没有找到； 2）即使存在有效的抗体，由于抗体和抗原形成的复合物 后无法再生，所以必须高剂量使用，限制其应用。 替代方法：阻断可卡因、鸦片与受体的结合； 抗体酶的优势：不但能和抗原结合，而且能在水解抗原后再生，这样既减少了用量，也能减少抗体酶的免疫原性。因此，抗体酶在戒毒方面拥有更