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

基本信息

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
项目类别：
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

项目摘要

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（但人类除外）的细胞表面。来自外源（例如，用于制造生物治疗产品的动物源性试剂）的潜在免疫原性 Neu5Gc 被人体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为治疗用途而培养的人体细胞。与此同时，所有人类也都有针对 Neu5Gc 的循环抗体，其中一些抗体水平非常高。因此，Neu5Gc 的存在可能导致功效降低、免疫排斥甚至针对治疗细胞或药物的免疫反应。 Neu5Gc 也从饮食来源（主要是红肉和奶制品）摄入并进入人体。此外，与食用红肉和奶制品相关的各种人类疾病（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）可能是由存在于同一食物中的 Neu5Gc 抗原和抗 Neu5Gc 抗体的组合引发的。人体。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。这笔特别资助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，我们建议优化用于在生物技术和生物医学研究应用中检测和测量 Neu5Gc 的多克隆抗体的生产和特异性；并开发小鼠单克隆抗体来检测和测量全谱的特定 Neu5Gc 含有表位。第一阶段将包括多克隆抗体的商业化，第二阶段建议产生额外的人类和/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众健康，从而开发出旨在检测和防止外来 Neu5Gc 掺入现象的产品。这种现象可能具有实际的生物医学意义，因为实验室发现所有人类的血液中都循环有针对 Neu5Gc 的抗体。因此，培养细胞和供人类使用的生物药品上存在免疫反应性 Neu5Gc 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