Detection of Non-Human Sialic Acid in Biotherapeutic Applications

生物治疗应用中非人类唾液酸的检测

• 批准号: 7928488
• 负责人: Elaine Anselmo Muchmore
• 金额: $ 3.43万
• 依托单位: SIAMAB THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-07 至 2011-03-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7928488
• 关键词: Abbreviations; Affinity; Animals; Antibodies; Antibody Formation; Antigens; Autoimmune Diseases; B-Lymphocytes; Binding; Biological Products; Biological Response Modifier Therapy; Biomedical Research; Biotechnology; Blood; CMP-N-acetylneuraminate monooxygenase; California; Cell Culture Techniques; Cell surface; Cells; Chickens; Cultured Cells; Detection; Diagnostics Research; Disease; Eating; Ensure; Enzyme-Linked Immunosorbent Assay; Epitopes; Flow Cytometry; Food; Freezing; Genes; Glycoconjugates; Grant; Health; Human; Human Genome; Human body; IgY; Immune; Immune response; Immunohistochemistry; Individual; Industry; Intention; Intravenous; Legal patent; Licensing; Malignant Neoplasms; Measures; Meat; Methods; Milk; Mono-S; Monoclonal Antibodies; Mus; Mutation; Myocardial Infarction; N-Acetylneuraminic Acid; Neuraminic Acids; Oligosaccharides; Pan Genus; Peritoneal; Pharmaceutical Preparations; Phase; Polysaccharides; Procedures; Process; Production; Protocols documentation; Public Health; Reagent; Research; Residual state; Sampling; Sialic Acids; Source; Specificity; Stroke; Structure; Surface; Techniques; Temperature; Therapeutic; Therapeutic Uses; Therapeutic antibodies; Tissue Sample; Tissues; Universities; Western Blotting; Work; base; carbene; commercialization; cytokine; design; embryonic stem cell; human disease; human tissue; humanized monoclonal antibodies; immunogenic; polyclonal antibody; prevent; small molecule; tissue culture

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

描述（由申请人提供）：GcFree, Inc.是基于一种名为Neu5Gc的唾液酸的最新发现和专利而成立的，这种唾液酸大量存在于大多数动物的细胞表面，而不是人类。来自外源的潜在免疫原性Neu5Gc（例如，用于制造生物治疗产品的动物源性试剂）被人类细胞吸收并在其表面表达，就像在这些细胞内产生一样。因此，Neu5Gc经常污染生物制药产品，以及用于治疗的人类细胞。与此同时，所有人类也都有针对Neu5Gc的循环抗体，有些抗体的水平非常高。因此，Neu5Gc的存在可能导致疗效降低、免疫排斥甚至对治疗细胞或药物的免疫反应。Neu5Gc也通过饮食来源（主要是红肉和奶制品）被摄入并纳入人体。此外，与食用红肉和奶制品有关的各种人类疾病（特别是心脏病、中风、几种常见癌症，以及可能的自身免疫性疾病）可能由同一人体中存在Neu5Gc抗原和抗Neu5Gc抗体的组合引发。这家新成立的公司专注于与这些发现引起的关键人类健康问题相关的许多商业机会。这项特别拨款的重点是在所有生物治疗应用以及正常和病理人体组织中检测Neu5Gc。因此，我们建议优化多克隆抗体的生产和特异性，以检测和测量Neu5Gc在生物技术和生物医学研究中的应用；并开发小鼠单克隆抗体，用于检测和测量含有Neu5Gc的特异性表位的全谱。第一阶段将包括多克隆抗体的商业化，第二阶段拟产生额外的人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，从而导致设计用于检测和预防外来Neu5Gc掺入现象的产品。这一现象很可能具有实际的生物医学意义，因为该实验室发现，所有人的血液中都有针对Neu5Gc的抗体。因此，在培养细胞和人用生物药物上存在免疫反应性Neu5Gc可能会导致治疗细胞或药物的疗效降低、免疫排斥甚至严重的免疫反应