Reverse phase chromatog. (RPC) is the most commonly and frequently used peptide separation technique but has its challenges, such as column fouling and limited resolution efficiency for hydrophilic and polar species.Addition of an orthogonal purification step, to both protect the RPC column and to increase the resolution, could solve these issues.In this case study we developed a two-step purification setup consisting of ion exchange (IEX)-RPC for a glycopeptide conjugate API, since the original RPC approach was not robust due to performance decay over time.First, screening conditions were used to show the proof-of-principle, later followed by a thorough large sample load optimization where focus was on identifying running conditions for the IEX and RPC steps to obtain a robust process scale setup.Then, purity and yield were evaluated for IEX-RPC vs.RPC-RPC.Since the main impurity in the glycopeptide API feed had similar hydrophobic properties as the target, the IEX-RPC setup outperformed the more traditional RPC-RPC setup, with a much higher obtained yield at similar purity.

Pre-purification of complex feeds using a high-salt tolerant AIEX resin prior to protein A chromatography

作者: Heijbel, Anna ; Carlbom, Lone ; Schonn, Mikael ; Unoson, Cecilia ; Berglof, jan

Purification of monoclonal antibodies (mAbs) expressed in bacteria or mammalian host cells, results in extensive bioburden on the protein A column, in the form of DNA and protein impurities when feed is directly loaded without major pre-treatments.To increase the lifetime of these sensitive protein A resins and to improve the final purity of the target mol., we have included an upstream multimodal AIEX column.This high-salt-tolerant AIEX provides protection for the protein A capture-step column by removing the majority of bulk impurities before the feed is loaded onto the sensitive resin, thus enhancing the lifetime of this resin.Placing a multimodal AIEX column upstream this column to capture impurities early in the process, bridge the more manual and tedious harvesting and pre-treatment steps with the down-stream purification steps.The majority of hazardous impurities such as host cell DNA/ chromatins, viruses and endotoxins from complex feeds are thus removed.We will present a case study where we have applied this concept.For the mAb purifications the usual three-step purification was performed but now the AIEX step (usually placed post-protein A) was instead placed upstream the protein A column.This re-placement of the purification steps in the mAb purification scheme is a novel concept called ECP, Enhanced Capture Process.The case study showed that this new upstream concept is highly efficient giving very pure final eluted target mols.Furthermore, this concept can also be applied to other applications, such as purification of insulin and other peptides and his-tagged proteins, to prolong the lifetime of resins used in the later purification steps, and also to increase the final purity of the target substance.

Peptide purifications using consistent buffer conditions in both ion exchange and reverse phase chromatography

作者: Heijbel, Anna ; Thorsen, Jenny ; Unoson, Cecilia

Reversed phase chromatog. (RPC) is often the first choice for peptide purifications when screening conditions at lab or anal. scales and usually generates high purities at high yields.It has some drawbacks however.Its delicate silica backbone has low tolerance to harsh cleaning conditions and can easily become fouled, causing difficulties in resolving some impurities and contaminants, such as polar analytes.To circumvent this problem an orthogonal hydrophilic resin, an agarose-based ion exchange resin (IEX), that tolerates harsh chems. can be introduced upstream of the RPC column.In this study we use a traditional RPC binding buffer, 0.1% TFA, pH 2, as the IEX binding buffer to bind peptides on a cation exchange resin since the peptide will be cationic - the amino acids are protonated - at such a low pH.Employing an acidic pH is advantageous since unknown sequences will be bound to the ligand on the CIEX resin (sulfonate ligand).We will present two case studies where we have tested the feasibility of this proposed generic IEX - RPC purificationThe two peptides studied had very different properties, on is a complex cyclic basic glucopeptide conjugate and the other one is a linear acidic peptide with low complexity (Bivalirudin).We loaded the peptide crudes (feed purities higher than 80%) onto a CIEX column and further onto an RPC column.We evaluated the purity and yield from this setup and compared it to using both columns as stand-alone columns.The glucopeptide conjugate feed had one very difficult to resolve impurity close to the main peak that was easily resolved on a CIEX resin.The early eluting impurities, the less hydrophobic impurities, which were not properly resolved on RPC were significantly reduced when CIEX was implemented upstream in the purifications, thus showing the orthogonality of these two methods.The combination of CIEX and RPC resulted in high purities and only a small yield loss.In conclusion, initial IEX runs are easily set up using RPC-compatible buffers for screening purposes.

116

项与 Bio-Works Technologies AB 相关的新闻（医药）

2024-10-17

·创鉴汇

AI制药领域35家公司Q3获得融资

今年的诺贝尔奖相继揭晓，人工智能（AI）无疑成为了焦点。AI学者不仅摘得了2024年诺贝尔物理学奖，诺贝尔化学奖也颁发给了三位与AI相关领域的科学家。谷歌DeepMind公司的Demis Hassabis博士和John Jumper博士，因其在蛋白质结构预测领域的突破性贡献获奖，他们的研究解决了这一领域50年来的重大挑战。与此同时，华盛顿大学的David Baker教授则因其在计算蛋白设计方面的卓越成就获此殊荣。这些AI驱动的科研成果极大地推动了生物医药领域的科学发现，也彰显了AI在制药领域的潜力和价值。在此背景下，AI制药行业也迎来了蓬勃发展。仅在2024年第三季度，全球至少有35家AI制药公司获得了总计超过10亿美元的融资。值得关注的亮点包括：早期融资占比过半：早期融资（B轮及以前）事件占比近70%；全球共有8家AI制药企业获A轮融资，总融资额超2亿美元，8家初创企业获得种子轮融资，总金额超5000万美元。 Flagship Pioneering先后推出两家新锐公司：Flagship分别投资5000万美元，孵化出了AI助力的基因药物递送平台Mirai Bio和可编程生物制剂研发公司Abiologics。公司类型多元：获得融资的公司中，业务类型涵盖小分子药物发现到细胞疗法研发的众多药物类型，并且以打造AI技术平台的平台型公司和专注于AI辅助药物管线发现的研发型公司数量平分秋色。 BioAge Labs成功登陆纳斯达克，IPO募资1.98亿美元 BioAge Labs是一家抗衰老研究公司，目前共有3个研究方向：代谢和肌肉衰老、免疫衰老和大脑衰老。公司致力于通过绘制人类衰老图谱并利用独有的AI药物发现平台，以开发治疗疾病和延长健康寿命的创新药物。BioAge Labs的主要候选药物Azelaprag是一种口服小分子药物，属于Apelin受体激动剂。该产品正在与礼来GLP-1/GI受体激动剂Tizepatide联合开展减肥2期临床试验，它还将于明年上半年与诺和诺德减肥产品Wegovy联合进入2期试验。 9月26日，BioAge Labs在纳斯达克上市，募资1.98亿美元，该融资所得将用于推动其减肥管线的临床试验。 Outpace Bio完成1.44亿美元B轮融资 Outpace Bio是一家细胞疗法公司，利用人工智能蛋白质设计对免疫细胞进行编程，以改善实体瘤患者体内功能。公司的技术平台致力于利用人工智能，设计具有自然界中没有的全新功能的蛋白和调控回路。并且利用这些全新蛋白和调控回路精密调节细胞的分化状态以及信号通路，从而让它们在合适的时间产生合适的作用。 Outpace Bio的主打项目OPB-101是一种针对间皮素的CAR-T细胞，利用Outpace的专有技术OUTSMART、OUTLAST、OUTSPACER和OUTSAFE进行增强，计划于2025年获得IND许可并首次在晚期铂耐药性上皮性卵巢癌、输卵管癌或原发性腹膜癌患者进行给药。 8月1日，公司宣布完成超额认购的B轮融资，筹集1.44亿美元，获得的资金将用于推进多种T细胞候选疗法，以期在实体肿瘤治疗中获得早期临床概念验证。此外，这些资金还将支持Outpace利用其模块化技术平台扩展未来的产品线。 Superluminal Medicines完成1.2亿美元A轮融资成立于2023年，Superluminal Medicines是一家致力于推动小分子药物研发的速度和准确性的开发差异化药物管线的生成生物和化学公司。公司利用深厚的生物学和化学专业知识、机器学习以及专有的大数据基础设施，快速开发创建候选化合物。平台采用预测-设计-测试架构，精确模拟蛋白质形状，并设计高度选择性的化合物，以达到治疗效果。公司由业内领先的AI药物发现上市公司Schrödinger前高管Cony D'Cruz先生和知名风投RA Capital Management的Ajay Yekkirala先生共同创立。目前，Superluminal的开发重点集中于高价值的G蛋白偶联受体（GPCR）靶点药物的开发。 9月9日，Superluminal Medicines公司宣布完成1.2亿美元的A轮融资。获得资金将用于支持该公司的主打在研项目进入临床开发，并增加针对GPCR靶点的小分子药物发现项目。 Circle Pharma完成9000万美元D轮融资 Circle Pharma是一家致力于包括口服等多种给药途径的细胞渗透性大环化合物的发现和开发的生物技术公司，其MXMO平台结合了基于结构的合理药物设计和先进的合成化学，开发了新一代大环疗法，用于靶向具有挑战性的靶点。目前公司将开发重点放在细胞周期蛋白上，这类蛋白是控制细胞在细胞周期中进展机制的主要调节器，也是许多癌症的关键驱动因素。 9月3日，Circle Pharma宣布完成9000万美元的D轮融资，此轮融资的资金将用于资助其细胞周期蛋白A/B（cyclin A/B）RxL抑制剂CID-078的临床开发。CID-078是一种多肽类抗肿瘤药物，目前处于早期临床阶段。 CytoReason获得8000万美元战略投资 CytoReason是一家致力于开发计算疾病模型的技术公司。该公司使用来自医药合作伙伴的真实数据来构建组织和细胞的特定模型以模拟各种疾病，然后利用其机器学习AI探索这些模型，能够突出不同患者群体和治疗方法之间的差异，潜在地为候选新药确定更有效的进攻路径。 CytoReason的平台是由70名经验丰富的生物学家、生物信息学家和数据工程师组成的多学科团队开发的。该平台使医药和生物技术公司能够优先考虑新目标、寻找生物标志物并预测哪些患者可能对新疗法产生最佳的反应，从而缩短试验阶段、降低开发成本并增加药物获批的可能性。 7月17日，公司宣布获得OurCrowd、英伟达（NVIDIA）、辉瑞（Pfizer）和赛默飞世尔（Thermo Fisher Scientific）总计8000万美元的融资。CytoReason将利用这笔投资将其模型的应用扩展到其他适应症，增加其专有的分子和临床数据。 Mirai Bio获5000万美元A轮融资 Mirai由Flagship Pioneering于2021年创立，旨在提供开源技术平台，与生物技术公司合作开发优化的基因药物（genetic medicines）。公司的技术平台包括高通量自动化、体内多重筛选、机器学习等前沿技术，能够产生大量数据并且通过优化的迭代循环，同时优化基因药物的递送、设计和生产，提高疗法开发的成功率和开发速度。 9月28日，公司宣布获得Flagship Pioneering的5000万美元A轮投资，资金将用于促进该公司技术平台的开发，以及在多个疾病治疗领域和治疗模式中加速基因药物的开发。 Flagship推出新锐公司Abiologics Abiologics是一家通过创造名为Synteins的可编程药物，重新定义生物制品的公司。Synteins是一种在自然界中不存在的全新药物类型，它通过计算设计生成，并使用新型的合成构建块，赋予其独特的特性，能够为各类疾病患者提供变革性的治疗。该公司的技术平台依托先进的生成式人工智能，从头计算设计Synteins，使用广泛的人工构建模块，突破了目前生物制品仅依赖20种天然氨基酸的局限。Synteins能够被编程从而与几乎所有治疗靶点相互作用，并且巧妙地规避身体的自然免疫防御机制。 7月24日，Flagship Pioneering初步承诺投资5000万美元以推进该公司的平台并开发多样化的药物管线，初步重点是肿瘤学和免疫学适应症。读者们请星标⭐创鉴汇，第一时间收到推送免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转发/复制至其他平台。转发授权请在「创鉴汇」微信公众号留言联系我们。更多数据内容推荐点击“在看”，分享创鉴汇健康新动态

临床申请临床2期细胞疗法IPO临床1期

2024-10-09

·PRNewswire

Nona Biosciences Enters Strategic Collaboration with OverT Bio to Advance Next-Generation Cell Therapies for Solid Tumors

CAMBRIDGE, Mass., Oct. 9, 2024 /PRNewswire/ -- Nona Biosciences, a global biotechnology company providing a total solution from "Idea to IND" (I to ITM), today announced a strategic collaboration with OverT Bio, a New York-based biotechnology company. The collaboration will focus on developing next-generation cell therapies for solid tumors by leveraging Nona's proprietary fully human HCAb Harbour Mice® platform and its innovative direct CAR-function-based HCAb library screening platform, NonaCarFxTM. The fully human heavy chain-only antibodies (HCAbs) generated from Nona's HCAb Harbour Mice® platform provide an ideal modality for CAR-based cell therapies. Unlike traditional methods, fully human HCAbs have the potential to significantly reduce immunogenicity. Their compact size, simplified structure, and precisely calibrated binding properties offer enhanced versatility in CAR design. In the evolving field of cell therapy, fully human HCAbs present significant potential to unlock further therapeutic advancements. "We are excited to partner with OverT Bio to advance novel cell therapies for solid tumors," said Jingsong Wang, MD, PhD, Chairman of Nona Biosciences. "By combining our fully human HCAb technology with OverT Bio's innovative approaches, we aim to accelerate the development of transformative therapies that have the potential to significantly improve patient outcomes." Mat Legut, PhD, CEO of OverT Bio, added, "We are excited to partner with Nona as we are advancing the field of genetically enhanced allogeneic gamma delta T cells. By leveraging Nona's fully human HCAbs, we are accelerating the development of our first clinical program to demonstrate the safety and efficacy of our differentiated cell engineering platforms." About Nona Biosciences Nona Biosciences is a global biotechnology company committed to cutting edge technology innovation and providing a total solution from "Idea to IND" (I to ITM), ranging from target validation and antibody discovery through preclinical research. The integrated antibody and antibody-related discovery services with multiple modalities range from antigen preparation, animal immunization, single B cell screening, to antibody lead generation and engineering, developability assessment and pharmacological evaluation, leveraging advantages of Harbour Mice® platforms and the experienced therapeutic antibody discovery team. Harbour Mice® generates fully human monoclonal antibodies in classical two light and two heavy chain (H2L2) format, and heavy chain only (HCAb) format. Integrating Harbour Mice® and a single B cell cloning platform, Nona Biosciences is focused on driving global inventions of transformative next-generation drugs. For more information, please visit: . About OverT Bio OverT Bio, Inc., is a New York based biotechnology company developing effective and safe cellular therapies for solid tumors. Harnessing innovative pooled functional screening and synthetic genomics platforms (OverTargetTM and OverTCRTM), OverT Bio is uncovering new therapeutic targets and genetic enhancements in an unbiased, data-driven manner to deliver breakthrough medicines to cancer patients underserved by the standard of care. For more information, please visit: . SOURCE Nona Biosciences WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

细胞疗法

2024-09-30

·医药魔方Pro

5000万美元！Flagship推出新公司，开发新型LNP技术

9月26日，Flagship Pioneering宣布推出一家名为Mirai Bio的新公司，该公司开创了生物技术行业首个开放的端到端基因药物平台。公司从Flagship Pioneering获得了5000万美元的初始投资。 Mirai由Flagship Pioneering于2021年创立，由拥有数十年基因药物创新经验的专家领导。Mirai基于机器智能（ML）的开放式平台使用专有的数据算法和机器智能来解锁任何组织和细胞类型的递送，优化载荷设计以及促进生产制造。递送、设计和制造的共同优化有可能使基因药物的成功概率更高，开发时间更快。以递送为例，目前基因药物的递送仅限于少数细胞类型，治疗窗口很窄。Mirai的平台旨在使任何组织及任何细胞类型的递送成为可能（下图）。据介绍，该公司已经开始改进用于疫苗递送和肝脏递送的脂质纳米颗粒（LNP），同时还在研究用于眼部、免疫细胞和骨髓造血干细胞的LNP。其他突破方向还包括开发实现脂肪细胞、中枢神经系统或骨骼肌有效递送的LNP。值得一提的是，不同于Flagship创办的大多数公司，Mirai Bio的发展战略不是围绕其递送平台建立自己的药物管线，而是将完全专注于与其他公司的合作。虽然Mirai不称自己为CDMO公司，但它并不否认这个标签至少部分准确。据悉，Mirai已经在生产用于临床前研究的药物。 “机器智能正在改变药物的发现和开发，其正在利用大量数据来推动未来最伟大的创新。基因药物的设计空间是无限的，Mirai正在为这一领域开创下一个巨大飞跃。”Mirai创始CEO、Flagship Pioneering普通合伙人Geoffrey von Maltzahn博士说道。参考资料： [1]https://www.miraibio.com/news/flagship-pioneering-unveils-mirai-bio-to-provide-fully-integrated-end-to-end-genetic-medicine-development-capabilities-for-the-biotech-industry [2]https://www.miraibio.com/#approach [3]https://endpts.com/flagship-launches-startup-to-design-and-make-lipid-nanoparticles-for-genetic-medicines/ Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

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