To benchmark the utility of E06: A half-life extension, single-domain, shark antibody bio-tool, and progress it to a Phase 1 ready candidate clone

对 E06 的实用性进行基准测试：一种半衰期延长、单域、鲨鱼抗体生物工具，并将其发展为第一阶段就绪的候选克隆

• 批准号: BB/K010905/1
• 负责人: Andrew Porter
• 金额: $ 55.49万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK010905%2F1
• 关键词: benchmark; utility; E06; half; life

Scientifically we are developing a "bio-tool" that could be fused to a range of different therapeutic proteins/peptides to extend their serum half-life from hours to weeks, with the potential of greatly increasing their therapeutic potency. It works by hitching a ride on other long-lived proteins in the blood. Commercially, our medium-term goal is to create a Drug Discovery company, based on our unique, single-domain shark antibody (VNAR) platform, which will develop therapeutic agents in-house or in partnership with larger companies. To achieve this, meeting of scientific milestones is key, and in particular confirming non-immunogenicity (not seen by the human immune system & safe for use), and validate the most advanced of our products (E06 VNAR half-life extension bio-tool). Progress towards this goal will also provide a platform for NewCo formation and equity raising, and will deliver an asset capable of securing multiple revenue streams of licensing and partnered income.

从科学上讲，我们正在开发一种“生物工具”，它可以与一系列不同的治疗蛋白/多肽融合，将它们的血清半衰期从几个小时延长到几周，并有可能极大地提高它们的治疗效力。它的工作原理是搭乘血液中其他长寿蛋白质的便车。在商业上，我们的中期目标是在我们独特的单域鲨鱼抗体(VNAR)平台的基础上创建一家药物发现公司，该平台将在内部或与较大公司合作开发治疗剂。要实现这一点，满足科学里程碑是关键，特别是确认非免疫原性(人类免疫系统看不到，使用安全)，并验证我们最先进的产品(E06 VNAR半寿命延长生物工具)。实现这一目标的进展还将为新公司的成立和股权融资提供一个平台，并将交付一项能够确保许可和合作收入的多种收入来源的资产。

项目成果

In Vitro Maturation of a Humanized Shark VNAR Domain to Improve Its Biophysical Properties to Facilitate Clinical Development.

• DOI: 10.3389/fimmu.2017.01361
• 发表时间: 2017
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Steven J;Müller MR;Carvalho MF;Ubah OC;Kovaleva M;Donohoe G;Baddeley T;Cornock D;Saunders K;Porter AJ;Barelle CJ
• 通讯作者: Barelle CJ

In Vitro ELISA and Cell-Based Assays Confirm the Low Immunogenicity of VNAR Therapeutic Constructs in a Mouse Model of Human RA: An Encouraging Milestone to Further Clinical Drug Development.

体外 ELISA 和基于细胞的测定证实 VNAR 治疗结构在人类 RA 小鼠模型中的低免疫原性：进一步临床药物开发的一个令人鼓舞的里程碑。

• DOI: 10.1155/2020/7283239
• 发表时间: 2020
• 期刊: Journal of immunology research
• 影响因子: 4.1
• 作者: Ubah OC

Structural insights and biomedical potential of IgNAR scaffolds from sharks.

• DOI: 10.4161/19420862.2015.989032
• 发表时间: 2015
• 期刊: mAbs
• 影响因子: 5.3
• 作者: Zielonka S;Empting M;Grzeschik J;Könning D;Barelle CJ;Kolmar H
• 通讯作者: Kolmar H

Anti-ICOSL New Antigen Receptor Domains Inhibit T Cell Proliferation and Reduce the Development of Inflammation in the Collagen-Induced Mouse Model of Rheumatoid Arthritis.

• DOI: 10.1155/2018/4089459
• 发表时间: 2018
• 期刊: Journal of immunology research
• 影响因子: 4.1
• 作者: O'Dwyer R;Kovaleva M;Zhang J;Steven J;Cummins E;Luxenberg D;Darmanin-Sheehan A;Carvalho MF;Whitters M;Saunders K;Barelle CJ
• 通讯作者: Barelle CJ

Therapeutic Potential of Shark Anti-ICOSL VNAR Domains is Exemplified in a Murine Model of Autoimmune Non-Infectious Uveitis.

• DOI: 10.3389/fimmu.2017.01121
• 发表时间: 2017
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Kovaleva M;Johnson K;Steven J;Barelle CJ;Porter A
• 通讯作者: Porter A