Mapping the Effect of Excess Fatty Acids on Albumin-Drug Interactions by NMR

Treature Biophma Inc.(简称Treature)已经开发出一种极具竞争力的产品，这里称为“TBI-HSA”，这是一种治疗性白蛋白，专为外科应用中的低血容量和控制肿瘤性压力而设计。治疗性白蛋白也在进行第三阶段的临床试验，这是基于它可能用于治疗阿尔茨海默病患者的痴呆症。TBI-HSA生物制剂是通过Cohn的混合人血浆分离获得的传统白蛋白的一种可行的替代品，由于加拿大人口的快速老龄化和手术期间对血浆生物制剂需求的预计增加，未来的增长前景非常好。为了充分利用Treature开发的技术在这些市场上增长的潜力，有必要在分子水平上了解TBI-HSA的制造工艺如何影响该配方的活性成分，即白蛋白蛋白。在这里，我们建议通过先进的核磁共振波谱方法来确定TBI-HSA制造过程的关键步骤-添加稳定剂以增强白蛋白稳定性-如何扰乱白蛋白与常见药物(如萘普生和华法林)的相互作用。考虑到这些相互作用的改变会影响白蛋白发挥非治疗作用的能力，核磁共振提供的分子图像将为治疗公司实施的制造工艺的未来优化提供信息。这种类型的优化将为Treure提供相对于其国际竞争对手的独特竞争优势，从而帮助Treure显著扩大其全球市场。然而，治疗公司目前无法获得获得这一竞争优势所需的专业核磁共振专业知识。梅拉西尼团队将提供必要的专业知识，因为梅拉西尼博士专门从事核磁共振对蛋白质的生物物理表征。应用这些核磁共振成像方法来监测TBI-HSA活性成分在制造过程中的变化，将使Treure进一步扩大其在血浆生物制品市场的份额。

Therapure Biopharma Inc. (or Therapure in short) already developed a highly competitive product, referred tohere as "TBI-HSA", which is a therapeutic albumin designed for the cost-effective treatment of hypovolemiaand the control of oncotic pressure in surgical applications. Therapeutic albumin is also undergoing phase IIIclinical trials based on its potential use for treating dementia in Alzheimer's patients. The TBI-HSA biologicsis a viable alternative to traditional albumins obtained through Cohn's fractionation of pooled human plasmaand the prospect of future growth is excellent due to the rapidly aging population of Canada and the projectedincrease in demand for plasma biologics during surgeries. In order to fully exploit the full potential of thetechnology developed by Therapure for growth in these markets, it is essential to understand at the molecularlevel how the manufacturing process of TBI-HSA affects the active ingredient of this formulation, i.e. thealbumin protein. Here, we propose to determine through advanced Nuclear Magnetic Resonance (NMR)spectroscopy methods how a critical step of the TBI-HSA manufacturing process, the addition of stabilizers toenhance albumin stability, perturbs the interactions of albumin with common drugs, such as naproxen andwarfarin. Considering that alteration in these interactions affects the ability of albumin to function as abiotherapeutic, the molecular images provided by NMR will inform the future optimization of themanufacturing process implemented by Therapure. This type of optimization will provide Therapure a uniquecompetitive edge relative to its international competitors and thus will help Therapure significantly expand itsworldwide market. However, Therapure currently has no access to the specialized NMR expertise required togain this competitive edge. The Melacini group will provide the necessary expertise, as Dr. Melacinispecializes in the biophysical characterization of proteins by NMR. The application of these NMR imagingmethodologies to monitor how the TBI-HSA active ingredient changes during the manufacturing process willallow Therapure to further expand its share in the plasma biologics market.