GOALI: Collaborative Research: Industrial Implementation of Smart Biopolymers for Purification of Biological Products

目标:合作研究:用于生物制品纯化的智能生物聚合物的工业实施

基本信息

  • 批准号:
    1403697
  • 负责人:
  • 金额:
    $ 29.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-09-01 至 2018-08-31
  • 项目状态:
    已结题

项目摘要

Karande, Pankaj / Chen, Wilfred 1403697 / 1403724 Rensselaer Polytechnic Institute / University of Delaware The proposed project is a collaboration between industry (Bristol-Myers Squibb) and academia (Rensselaer Polytechnic Institute and University of Delaware) aimed at developing the next generation and state-of-art smart biopolymers system for the purification of protein therapeutics in industrial bioprocessing. There is a significant need and interest in the industry for the development of novel techniques for recovery of biological materials that are advantageous in terms of scale, cost, and ease-of-deployment compared to conventional chromatographic processes. The PIs propose to develop affinity precipitation processes that combine the selectivity of affinity chromatography along with the scalability and cost benefits of precipitation. This project will employ new classes of affinity peptides in concert with efficient smart biopolymers which can be induced to come in and out of solution with minor changes in salt and/or temperature. There is significant interest in the development of non-chromatographic affinity recovery processes for biological products. Affinity precipitation combines the selectivity of affinity chromatography along with the scalability and cost benefits of precipitation. In prior research supported by NSF th PIs have employed Elastin like polypeptides fused to the mAb binding Z domain (ELP-Z) to develop a scalable mAb affinity precipitation method. The proposed work builds upon the previous work to generate entirely new classes of smart biopolymer affinity reagents and evaluate their utility for the industrial purification of mAbs, FCfusions, and non-mAb biologics from inclusion body and pegylation processes. Their practical utility will be evaluated for large-scale protein purification in partnership with Bristol-Myers Squibb (BMS). This research will result in a flexible platform for large-scale purification of biological products. The first component of the proposed project will be a new approach for affinity precipitation of mAbs and Fc fusion proteins under milder operating conditions using ZELP-E2 nanocages. The second component of the project will develop novel peptide affinity ligands for two classes of non-mAb proteins provided by our industrial collaborator BMS. The affinity peptides will then be employed in affinity precipitation formats to selectively capture the products from challenging feed stocks such as refolded protein pools and post-pegylation reaction mixtures. This work brings together Co-PIs with diverse expertise in protein engineering, peptide affinity design, affinity precipitation and downstream bioprocessing to develop entirely new classes of affinity precipitation reagents (Z-ELP-E2 nanocages, ELPaffinity peptides, and polyvalent affinity capture E2-(xAPy-ELP)) which if successful may result in a new integrated platform that will greatly simplify the recovery and purification of biological products. The proposed research could have a dramatic impact on the affinity capture of a broad range of therapeutic products represented by monoclonal antibodies, fusion proteins, biologics from inclusion bodies, and pegylated proteins. The combination of these novel technologies could represent entirely new approaches for the downstream processing of biologics with significant long-term industrial impact. Success in this work could not only impact the processing of difficult to recover and synthetically modified biologics but may also establish new paradigms for the bioprocessing of a wide range of many new biologics in development. This collaboration between academia and industry will serve as a proof-of-concept study for the potential industrial implementation of this transformative technology for the purification of biological products. Mechanisms for impact on education via graduate, undergraduate and K12 inclusion in research opportunities are discussed. This proposed molecular level and macroscopic separations level training is highly sought after by the biotechnology industry.
Karande,Pankaj / Chen,Wilfred 1403697 / 1403724伦斯勒理工学院/特拉华州大学拟议的项目是工业界(百时美施贵宝)和学术界(伦斯勒理工学院和特拉华州大学)之间的合作,旨在开发下一代和最先进的智能生物聚合物系统,用于工业生物加工中蛋白质治疗剂的纯化。在工业中存在对开发用于回收生物材料的新技术的显著需求和兴趣,与常规色谱方法相比,该技术在规模、成本和易于部署方面是有利的。PI建议开发亲和沉淀工艺,将亲和色谱的选择性沿着沉淀的可扩展性和成本效益相结合。该项目将采用新型亲和肽与有效的智能生物聚合物相结合,这些生物聚合物可以通过盐和/或温度的微小变化被诱导进出溶液。人们对开发用于生物制品的非色谱亲和回收方法非常感兴趣。亲和沉淀结合了亲和色谱的选择性沿着沉淀的可扩展性和成本效益。在由NSF支持的先前研究中,PI已经使用与mAb结合Z结构域(ELP-Z)融合的弹性蛋白样多肽来开发可扩展的mAb亲和沉淀方法。拟议的工作建立在以前的工作,以产生全新类别的智能生物聚合物亲和试剂,并评估其实用性的工业纯化的单克隆抗体,FCfusions,和非单克隆抗体生物制剂的包涵体和聚乙二醇化过程。将与百时美施贵宝公司(BMS)合作,对它们的实际效用进行大规模蛋白质纯化评估。这项研究将为生物产品的大规模纯化提供一个灵活的平台。拟议项目的第一个组成部分将是一种新的方法,用于在温和的操作条件下使用ZELP-E2纳米笼亲和沉淀mAb和Fc融合蛋白。该项目的第二部分将为我们的工业合作者BMS提供的两类非mAb蛋白开发新型肽亲和配体。然后,亲和肽将以亲和沉淀形式使用,以选择性地捕获来自挑战性原料如重折叠蛋白质池和聚乙二醇化后反应混合物的产物。这项工作汇集了在蛋白质工程,肽亲和设计,亲和沉淀和下游生物加工方面具有不同专业知识的Co-PI,以开发全新类别的亲和沉淀试剂(Z-ELP-E2纳米笼,ELP亲和肽和多价亲和捕获E2-(xAPy-ELP)),如果成功,可能会产生一个新的集成平台,大大简化生物产品的回收和纯化。拟议的研究可能会对以单克隆抗体、融合蛋白、包涵体生物制剂和聚乙二醇化蛋白为代表的广泛治疗产品的亲和捕获产生巨大影响。这些新技术的结合可能代表生物制品下游加工的全新方法,具有重大的长期工业影响。这项工作的成功不仅可以影响难以回收和合成改性生物制剂的加工,而且还可以为开发中的许多新生物制剂的生物加工建立新的范例。学术界和工业界之间的这种合作将作为一种概念验证研究,用于这种用于生物产品纯化的变革性技术的潜在工业实施。讨论了通过研究生、本科生和K12纳入研究机会对教育产生影响的机制。这种提出的分子水平和宏观分离水平的培训受到生物技术行业的高度追捧。

项目成果

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Pankaj Karande其他文献

LOCATE reveals electrostatic “islands” and “hotspots” are important for a disordered clock protein's interactions to regulate clock robustness
  • DOI:
    10.1016/j.bpj.2021.11.1731
  • 发表时间:
    2022-02-11
  • 期刊:
  • 影响因子:
  • 作者:
    Meaghan S. Jankowski;Daniel Griffith;Divya G. Shastry;Jacqueline F. Pelham;Joshua Thomas;Pankaj Karande;Alex S. Holehouse;Jennifer M. Hurley
  • 通讯作者:
    Jennifer M. Hurley

Pankaj Karande的其他文献

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{{ truncateString('Pankaj Karande', 18)}}的其他基金

Collaborative Research: Design of Peptide Crystal Growth Modifiers Using Experiments and Simulations
合作研究:利用实验和模拟设计肽晶体生长调节剂
  • 批准号:
    1207411
  • 财政年份:
    2012
  • 资助金额:
    $ 29.96万
  • 项目类别:
    Continuing Grant

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