ISOBIOTICS: Isotopic Labeling of Biotherapeutics

ISOBIOTICS：生物治疗药物的同位素标记

• 批准号: EP/X039501/1
• 负责人: Benjamin Davis
• 金额: $ 33.8万
• 依托单位: Rosalind Franklin Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX039501%2F1
• 关键词: ISOBIOTICS; Isotopic; Labeling; Biotherapeutics

Biological drugs such as peptides, proteins, oligonucleotides and analogs provide the patients with more efficacious and less toxic treatments and have lower attrition rates than chemical drugs since 1 on 9 new biological entities entering clinical trials reaches the market (1 on 16 for chemical drugs). Consequently, 15 on 24 top blockbuster drugs were biotherapeutics in 2020 (world-market share of about 40% of $175 billion of revenue per year). In order to reduce the immunogenicity of biodrugs, to overcome their fragility and to increase their capacity to reach quickly and massively their target, reduced-size biologics are extensively developed. However, radiolabeling of large molecules by grafting bifunctional chelating agents which do not alter significantly their biological activity is thus no longer possible with smaller biodrugs. It is therefore of paramount importance to devise new radiolabeling approaches carried out on tiny quantities in aqueous media and very soft conditions. It is also crucial to train a new generation of radiochemists in order to implement these methods and to meet the needs of the European industry. ISOBIOTICS ambitions: 1) to develop new chemically-benign strategies for the last-stage radiolabeling of large peptides, small/medium-size proteins, oligonucleotides and analogs with deuterium, tritium and carbon-14 (preclinical and phase 0 clinical evaluation), and fluorine-18 (phase I-III clinical trials); 2) to educate a new generation of young talented PhD students specialized in the radiolabeling of biologics through a combination of interdisciplinary lab research, transdisciplinary and intersectorial secondments, technical taught courses, scientific lectures and complementary skills workshops; 3) to ensure the appropriate dissemination, exploitation and communication of all ISOBIOTICS outputs in order to maximize the project's impact and radiance; 4) to secure the students employment and the sustainability of training structures.

肽、蛋白质、寡核苷酸和类似物等生物药物为患者提供了更有效、毒性更小的治疗方法，并且比化学药物具有更低的损耗率，因为进入临床试验的新生物实体有 1:1 进入市场（化学药物为 1:16） 。因此，到 2020 年，24 种顶级重磅药物中有 15 种是生物治疗药物（全球市场份额约为每年 1,750 亿美元收入的 40%）。为了降低生物药物的免疫原性，克服其脆弱性并提高其快速、大量到达目标的能力，人们广泛开发了小型生物制剂。然而，通过接枝双功能螯合剂对大分子进行放射性标记不会显着改变其生物活性，因此对于较小的生物药物来说不再是可能的。因此，设计在水介质和非常柔软的条件下进行微量放射性标记的新方法至关重要。培训新一代放射化学家以实施这些方法并满足欧洲工业的需求也至关重要。 ISOBIOTICS 的目标：1) 开发新的化学良性策略，用于大肽、小/中型蛋白质、寡核苷酸以及氘、氚和碳 14 类似物的最后阶段放射性标记（临床前和 0 期临床评估），以及氟18（I-III期临床试验）； 2) 通过跨学科实验室研究、跨学科和跨部门借调、技术教学课程、科学讲座和补充技能讲习班相结合，教育专门从事生物制品放射性标记的新一代年轻有才华的博士生； 3) 确保所有 ISOBIOTICS 成果的适当传播、利用和交流，以最大限度地发挥项目的影响和光芒； 4）确保学生就业和培训结构的可持续性。