'Knob' antibody fragments (Picobodies™) derived from cows could define new therapeutic class

'旋钮'抗体片段（Picobodies™) 来源于奶牛可以定义新的治疗类别

SAN DIEGO, Sept. 20, 2023 /PRNewswire/ -- A collaborative scientific team led by researchers at the Applied Biomedical Science Institute (ABS), Scripps Research, Kansas State University (K-State), University of Louisville, OmniAb, Inc., and Ligand Pharmaceuticals has discovered and validated a potential new class of therapeutic agent based on the unique antigen binding regions of cow antibodies.

2023年9月20日，圣地亚哥/PRNewswire/-由应用生物医学科学研究所（ABS），堪萨斯州立大学斯克里普斯研究所（K-State），路易斯维尔大学，OmniAb，Inc。的研究人员领导的合作科学团队配体药物已经发现并验证了一种潜在的新型治疗剂，它基于牛抗体的独特抗原结合区域。

In their paper published in the Proceedings of the National Academy of Sciences, 'The smallest functional antibody fragment: ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2', the team of researchers discovered cow antibodies with broad reactivity and high potency against several SARS-CoV-2 virus variants.

在他们发表在美国国家科学院院刊上的论文中，“最小的功能性抗体片段：超长CDR H3抗体旋钮区域有效地中和SARS-CoV-2”，研究小组发现了具有广泛反应性和高效力的牛抗体。针对几种SARS-CoV-2病毒变种。

They then developed the technology to produce only the coronavirus binding portion of the antibody, termed a 'knob' region, which is a tiny fragment of the large parent antibody. 'At about 3% the size of the original antibody, cow knob regions represent the smallest known functional antibody fragment.

然后，他们开发了仅产生抗体的冠状病毒结合部分的技术，称为“旋钮”区域，其是大亲本抗体的微小片段在原始抗体大小的约3%处，cow旋钮区域代表最小的已知功能性抗体片段。

They approach the size of some small molecule drugs and are three times smaller than camel antibody-derived 'nanobodies'. Knobs potentially have many biomedical uses, including as therapeutics and diagnostics,' said Dr. Vaughn Smider, the senior author of the study and President of ABS. Potential advantages of such small antibody fragments include improved tissue penetration, clearance, and stability.

它们接近一些小分子药物的大小，比骆驼抗体衍生的“纳米抗体”小三倍。该研究的资深作者和ABS总裁Vaughn Smider博士说，旋钮可能具有许多生物医学用途，包括治疗和诊断。这种小抗体片段的潜在优点包括改善的组织穿透性，清除率和稳定性。

While the current study reveals the utility of knobs in targeting coronavirus, their potential as a therapeutic class spans many therapeutic areas, including oncology and immunology. Future research applications of knobs include using them as targeting regions for nanoparticles, antibody drug conjugates or multispecific therapeutics..

虽然目前的研究揭示了旋钮在靶向冠状病毒方面的效用，但它们作为治疗类的潜力涵盖了许多治疗领域，包括肿瘤学和免疫学。旋钮的未来研究应用包括将它们用作纳米颗粒，抗体-药物缀合物或多特异性治疗剂的靶向区域。。

The antibodies and derivative knob regions were induced in cows by Dr. Waithaka Mwangi's laboratory at K-State, and discovered and evaluated at ABS by first author Ruiqi Huang and a team of scientists at ABS, then characterized for anti-viral properties by the laboratories of Drs. Kyeong-Ok Chang (K-State), Donghoon Chung (Louisville), John Teijaro (Scripps Research), and Dennis Burton (Scripps Research), and detailed structural characterization was accomplished at Scripps Research in the laboratories of Drs.

抗体和衍生旋钮区域由K-State的Waithaka Mwangi博士实验室在奶牛中诱导，并由第一作者Ruiqi Huang和ABS的一组科学家在ABS中发现和评估，然后由实验室表征抗病毒特性。Kyeong-Ok-Chang博士（K-State），Donghoon Chung（路易斯维尔），John Teijaro（Scripps Research），和Dennis Burton（Scripps Research），详细的结构表征是在Drs实验室的Scripps Research中完成的。

Ian Wilson, Robyn Stanfield, Andrew Ward, Jane Dyson and Peter Wright. Industry collaborators led by Dr. William Harriman at OmniAb, Inc., and Dr. Jeff Allen at Pelican, a subsidiary of Ligand Pharmaceuticals collaborated in the analytical characterization and the manufacturing of the knobs. Minotaur Therapeutics (an ABS spin-out company) is developing commercial technologies related to knob region (picobody) discovery and development under a sublicense from OmniAb, Inc..

Ian Wilson，Robyn Stanfield，Andrew Ward，Jane Dyson和Peter Wright。由OmniAb，Inc。的William Harriman博士和Ligand Pharmaceuticals的子公司Pelican的Jeff Allen博士领导的行业合作者合作进行了分析表征和旋钮的制造。Minotaur Therapeutics（一家ABS spin out公司）正在OmniAb，Inc.的子许可下开发与旋钮区域（picobody）发现和开发相关的商业技术。。

See the original study at:

请参阅以下原始研究：

Huang, R. et.al. The smallest functional antibody fragment: ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2.  Proc. Natl. Acad. Sci. 120, e2303455120 (2023)

Huang，R。等。最小的功能性抗体片段：超长CDR H3抗体旋钮区域有效地中和SARS-CoV-2.Proc。国家科。科学院。科学。120，e2303455120（2023）

www.pnas.org/doi/10.1073/pnas.2303455120

www.pnas.org/doi/10.1073/pnas.2303455120

About Picobodies

关于Picobodys

Picobodies are isolated antibody 'knob' domains comprised of cysteine-rich ultralong complementary determining region (CDR) H3 sequences of 30-40 amino acids, which have the potential to access challenging epitopes better than full size antibodies.

Picobodies是由30-40个氨基酸的富含半胱氨酸的超长互补决定区（CDR）H3序列组成的分离的抗体“旋钮”结构域，其具有比全尺寸抗体更好地获得具有挑战性的表位的潜力。

About the Applied Biomedical Science Institute

关于应用生物医学科学研究所

The Applied Biomedical Science Institute (ABS) is a 501(c)(3) non-profit organization taking a leading role in basic research and its rapid clinical translation by performing cutting-edge basic and translational research. With deep expertise in antibody genetics, biology, engineering, and discovery technologies, ABS promotes therapeutic and diagnostic translation through their own internal research, collaborations, or licensing activities.

应用生物医学研究所（ABS）是一家501（c）（3）非营利性组织，通过进行尖端的基础研究和转化研究，在基础研究及其快速临床翻译方面发挥主导作用。ABS在抗体遗传学，生物学，工程和发现技术方面拥有丰富的专业知识，通过自己的内部研究，合作或许可活动促进治疗和诊断翻译。

ABS also trains early-stage researchers in biomedical research through post-doctoral fellow and internship programs..

ABS还通过博士后研究员和实习计划培训生物医学研究的早期研究人员。。

For more information, please visit https://absinstitute.org/

欲了解更多信息，请访问https://absinstitute.org/

About OmniAb®

关于OmniAb®

OmniAb's discovery platform provides pharmaceutical industry partners access to diverse antibody repertoires and high-throughput screening technologies to enable discovery of next-generation therapeutics. At the heart of the OmniAb platform is the Biological Intelligence™ (BI) of its proprietary transgenic animals, including OmniRat®, OmniChicken® and OmniMouse® that have been genetically modified to generate antibodies with human sequences to facilitate development of human therapeutic candidates.

OmniAb的发现平台为制药行业合作伙伴提供了多种抗体库和高通量筛选技术，以发现下一代治疗药物。OmniAb平台的核心是生物智能™ （BI）其专有的转基因动物，包括OmniRat®，Omnichick®和OmniMouse®，这些动物经过基因修饰以产生具有人类序列的抗体，以促进人类治疗候选物的开发。

OmniFlic® (transgenic rat) and OmniClic® (transgenic chicken) address industry needs for bispecific antibody applications though a common light chain approach, and OmniTaur™ features unique structural attributes of cow antibodies for complex targets. OmniAb believes the OmniAb animals comprise the most diverse host systems available in the industry and they are optimally leveraged through computational antigen design and immunization methods, paired with high-throughput single B cell phenotypic screening and mining of next-generation sequencing datasets with custom algorithms to identify fully human antibodies with superior performance and developability characteristics.

OmniFlic®（转基因大鼠）和OmniClic®（转基因鸡）通过常见的轻链方法满足双特异性抗体应用的行业需求，OmniTaur™ 具有用于复杂靶标的牛抗体的独特结构属性。OmniAb认为OmniAb动物包含该行业中可用的最多样化的宿主系统，并且它们通过计算抗原设计和免疫方法得到最佳利用，与高通量单B细胞表型筛选和使用定制算法挖掘下一代测序数据集相结合，以鉴定具有优异性能和可开发性特征的完全人抗体。

These proprietary technologies are joined with and leverage OmniDeep™, which is a suite of in silico tools for therapeutic discovery and optimization that are woven throughout OmniAb's various technologies and capabilities. Additionally, an established core competency focused on ion channels and transporters further differentiates OmniAb's technology and creates opportunities in many emerging target classes.

这些专有技术与OmniDeep结合并利用™, 这是一套用于治疗发现和优化的计算机软件工具，贯穿OmniAb的各种技术和功能。此外，专注于离子通道和转运蛋白的既定核心能力进一步区分了OmniAb的技术，并为许多新兴目标类别创造了机会。

OmniAb antibodies have been leveraged across modalities, including bispecific antibodies, antibody-drug conjugates and others..

OmniAb抗体已被用于各种形式，包括双特异性抗体，抗体-药物偶联物等。。

The OmniAb suite of technologies span from BI-powered repertoire generation to cutting-edge antibody discovery and optimization offering a highly efficient and customizable end-to-end solution for the growing discovery needs of the global pharmaceutical industry.

OmniAb系列技术从双功能曲目生成到尖端抗体发现和优化，为全球制药行业日益增长的发现需求提供高效和可定制的端到端解决方案。

For more information, please visit www.omniab.com.

欲了解更多信息，请访问www.omniab.com。

'Picobody' is a trademark of Crystal Bioscience, Inc., a subsidiary of OmniAb, Inc.

'Picobody'是OmniAb，Inc。的子公司Crystal Bioscience，Inc。的商标。

Nathalie NguyenApplied Biomedical Science Institute(858) 346-6300[email protected]

Nathalie NguyenApplied Biomedical Science Institute（858）346-6300[电子邮件保护]

SOURCE Applied Biomedical Science Institute

来源应用生物医学研究所