Detection of Non-Human Sialic Acid in Biotherapeutic Applications

描述（由申请人提供）：GcFree，Inc.它是建立在最近发现的一种叫做Neu 5Gc的唾液酸的专利上的，这种唾液酸大量存在于大多数动物的细胞表面，但不存在于人类。来自外源性来源的潜在免疫原性Neu 5Gc（例如，用于制备生物制品的动物源性试剂）被人细胞吸收并在其表面上表达，就好像在这些细胞内产生一样。因此，Neu 5Gc经常污染生物制药产品以及培养用于治疗用途的人类细胞。与此同时，所有人都有抗Neu 5Gc的循环抗体，有些抗体的水平非常高。因此，Neu 5Gc的存在可导致针对治疗性细胞或药物的功效降低、免疫排斥或甚至免疫应答。Neu 5Gc也可以从饮食来源摄入并融入人体，主要来自红肉和奶制品。此外，与食用红肉和乳制品相关的各种人类疾病（特别是心脏病发作、中风、几种常见癌症和可能的自身免疫性疾病）可以通过在同一人体中存在的Neu 5Gc抗原和抗Neu 5Gc抗体的组合来触发。这家新成立的公司专注于与这些发现所产生的关键人类健康问题相关的许多商业机会。这项特殊的资助重点是在所有生物医学应用以及正常和病理人体组织中检测Neu 5Gc。因此，我们建议优化用于在生物技术和生物医学研究应用中检测和测量Neu 5Gc的多克隆抗体的生产和特异性;并开发用于检测和测量特异性含Neu 5Gc表位的全谱的小鼠单克隆抗体。第1阶段将包括多克隆抗体的商业化，第2阶段计划生产额外的人和/或人源化单克隆抗体，并完成所有产品的商业化。这项研究工作将影响公共卫生，从而产生旨在检测和预防外源Neu 5Gc掺入现象的产品。这种现象可能具有实际的生物医学相关性，因为实验室发现所有人的血液中都有抗Neu 5Gc的抗体。因此，培养细胞和供人类使用的生物制药上存在免疫反应性Neu 5 Gc可能会导致功效降低、免疫排斥甚至针对治疗细胞或药物的严重免疫反应

DESCRIPTION (provided by applicant): GcFree, Inc. is founded on recent discoveries and patents about a sialic acid called Neu5Gc, which is present in large amounts on the surface of cells of most animals, but not humans. Potentially immunogenic Neu5Gc from exogenous sources (e.g., animal- derived reagents used for making biotherapeutic products) are taken up by human cells and expressed on their surfaces, as if produced within those cells. Thus, Neu5Gc frequently contaminates biopharmaceutical products, as well as human cells cultured for therapeutic use. Meanwhile, all humans also have circulating antibodies against Neu5Gc, some at very high levels. Thus, the presence of Neu5Gc could result in reduced efficacy, immune rejection or even immune responses against therapeutic cells or drugs. Neu5Gc is also being ingested and incorporated into the human body from dietary sources, primarily from red meats and milk products. Furthermore, various human diseases associated with eating red meat and milk products (particularly heart attacks, strokes, several common cancers, and possibly autoimmune diseases) could be triggered by the combination of having the Neu5Gc antigen and the anti-Neu5Gc antibodies present in the same human body. This newly founded company focuses on many commercial opportunities related to critical human health issues arising from these discoveries. This particular grant focuses on detecting Neu5Gc in all biotherapeutic applications and in normal and pathological human tissues. Thus, we propose to optimize production and specificity of polyclonal antibodies for detecting and measuring Neu5Gc in biotechnology and biomedical research applications; and develop mouse monoclonal antibodies for detecting and measuring the full spectrum of specific Neu5Gc- containing epitopes. Phase 1 will include commercialization of the polyclonal antibodies and Phase 2 proposes to generate additional human and/or humanized monoclonal antibodies, and to complete the commercialization of all products. This research effort will impact public health to leading to products designed to detect and prevent foreign Neu5Gc -incorporation phenomenon . This phenomenon is likely to be of practical biomedical relevance, because the lab has found that all humans also have antibodies against Neu5Gc circulating in their blood. Thus, the presence of immunoreactive Neu5Gc on cultured cells and biopharmaceuticals intended for human use is likely to result in reduced efficacy, immune rejection or even serious immune responses against the therapeutic cells or drugs