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：
7394889
负责人：
Elaine Anselmo Muchmore
金额：
$ 16.78万
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 2010-03-06
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7394889
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 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 Pan troglodytes Peritoneal Pharmaceutical Preparations Phase Polysaccharides Procedures Process Production Protocols documentation Public Health Range Reagent Research Residual state Sampling Sialic Acids Source Specificity Standards of Weights and Measures 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。建立在有关唾液酸NEU5GC的最新发现和专利上，该盐酸在大多数动物的细胞表面上大量存在，但不是人类。来自外源源的潜在免疫原性NEU5GC（例如，用于生产生物疗法产物的动物衍生试剂）被人类细胞吸收并在其表面上表达，就好像在这些细胞中产生的一样。因此，Neu5GC经常污染生物药物的产品，以及用于治疗用途的人类细胞。同时，所有人类还具有针对NEU5GC的循环抗体，其中一些抗体在很高的水平上。因此，NEU5GC的存在可能导致对治疗细胞或药物的疗效，免疫排斥或什至免疫反应。 Neu5GC还通过饮食来源（主要是来自红肉和牛奶产品）摄入并纳入人体。此外，可能会触发与食用红肉和牛奶产品相关的各种人类疾病（尤其是心脏病发作，中风，几种常见的癌症以及可能的自身免疫性疾病），这可能是通过具有NEU5GC抗原和抗-Neu5GC抗体的组合来触发的。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有关的许多商业机会。这项特殊赠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，以检测和测量生物技术和生物医学研究应用中的NEU5GC；并开发小鼠单克隆抗体，用于检测和测量含有特定neu5gc的表位的整个光谱。第1阶段将包括对多克隆抗体的商业化，第2阶段提议生成其他人类和/或人源化的单克隆抗体，并完成所有产品的商业化。这项研究工作将影响公共卫生，从而导致旨在检测和防止外国NEU5GC企业现象的产品。这种现象可能具有实用的生物医学相关性，因为该实验室发现所有人类也具有针对neu5GC循环的抗体。因此，旨在人类使用的培养细胞和生物药物上存在免疫反应性NEU5GC可能会导致疗效，免疫排斥或什至对治疗细胞的严重免疫反应降低