High throughput camelid antibody screening as drug discovery platform

描述(申请人提供)：单抗用于治疗从癌症到传染病的多种疾病。然而，开发高亲和力和高特异性的抗体仍然是耗时、费力和不可预测的。Abzyme Treateutics LLC正在积极开发无动物抗体发现平台，以加快治疗性抗体的生成。在第一阶段，我们将创建一个所谓的自我多样化抗体库或SDALib，作为一个单抗生成系统，它将在体外提供多样化的完整抗体阵列，而不使用免疫。该系统的主要特点是能够通过以下方式自行生成具有多种抗体的细胞库 抗体编码基因的高突变诱导手段。使用SDALib系统，针对任何抗原的单抗的产生时间将减少到大约两周，而使用传统技术通常需要6至9个月。该平台适用于同时筛选针对不同靶抗原的多种抗体。由于不需要对整个动物进行免疫，SDALib系统可以产生针对毒素、病原体、自身抗原等的特异性抗体，这些抗体在过去是很难获得的。作为一项原则证明，我们将开发能够抑制不同亚型甲型流感病毒神经氨酸酶(NA)的酶活性的骆驼单域抗体。一旦获得，候选抗体将被人源化，以降低对人类的免疫原性。多价和多特异性抗体将以线性融合的形式产生，以增加抗NA的效力和交叉反应。这种抗NA抗体可以作为鼻腔喷雾剂的一种成分，通过在第二阶段阻止流感病毒的传播来治疗流感。

DESCRIPTION (provided by applicant): Monoclonal antibodies are used for treatment of a wide range of diseases from cancer to infectious diseases. However, development of antibodies with high affinity and specificity is still time-consuming, labor-intensive and unpredictable. Abzyme Therapeutics LLC is actively developing animal-free antibody discovery platforms to accelerate generation of therapeutic antibodies. In Phase I, we will create a so-called Self-Diversifying Antibody Library or SDALib as a monoclonal antibody generating system that will provide a diverse array of complete antibodies in vitro, without using immunization. The main feature of the system is the ability to self-generate a cell library with diversified antibodies by means of hypermutation induction in antibody encoding genes. Using the SDALib system, generation time of monoclonal antibodies against any antigen will be reduced to about two weeks as compared to 6 to 9 months normally required using conventional techniques. The platform is adaptable for simultaneous screening for multiple antibodies specific for different target antigens. Since there is no need to immunize whole animals, the SDALib system can generate specific antibodies against toxins, pathogens, self-antigens, and the like which were by nature difficult to obtain in the past. As a proof-of-principle, we will develop camelid single domain antibodies capable of inhibiting the enzymatic activity of influenza A virus neuraminidases (NA) of different suptypes. Once obtained, candidate antibodies will be humanized to reduce immunogenicity in humans. Multivalent and multi-specific antibodies will be produced as linear fusions to increase anti-NA potency and cross-reactivity. Such anti-NA antibodies can be used as a component of a nasal spray for flu treatment by stopping the spread of the flu virus in Phase II.