NOVEL ENZYME FORMULATION FOR TREATMENT OF HYPEROXALURIA

说明书(申请人提供)：新型高效药物输送的设计 蛋白质系统是现代生物技术的主要主题之一， 生物制药行业。我们发现，交联酶晶体(CLECs) 在低pH条件下表现出稳定性，在储存和抗蛋白质降解方面表现出稳定性。这些 它们的特性使其成为肠腔治疗的理想选择。病人会吞下一颗 由所需代谢组成的CLEC颗粒的片剂或液体悬浮液 酶或蛋白质。CLEC试剂可以在苛刻的酸性pH和 胃的蛋白质分解环境，并通过近端的小 肠子。然后，CLEC颗粒将进行其治疗生物化学 在肠腔内，同时保持对内源性降解的抵抗 蛋白酶。在这项第一阶段研究中，我们建议发展两种类型的CLEC： 用于口腔腔治疗的草酰-辅酶A脱羧酶和草酸氧化酶 用于体外装置/透析设备。草酰辅酶A 脱羧酶-CLEC将在十二指肠内执行其作用，同时保持为 结晶物质或通过溶解CLEC释放活性 粒子。选择这个目标是为了解决目前治疗方法的问题。 由于缺乏草酸而过度吸收草酸而导致的高草酸 产草杆菌肠内或因肠炎引起的细菌 疾病。此外，草酸氧化酶-CLEC可用于透析设备或 体外循环装置降低慢性阻塞性肺疾病患者血液草酸含量的研究 原发性高草酸尿症。如果成功，这些方法将导致 介绍预防草酸的新型高效酶疗法 肾结石。 建议的商业应用：不可用

DESCRIPTION (provided by applicant): Design of new efficient drug delivery systems for proteins is one of the major themes of modern biotechnology and biopharmaceutical industry. We found that crosslinked enzyme crystals (CLECs) show stability under low pH, on storage and against proteolysis. These properties make them ideal for gut lumenal therapy. The patient would swallow a tablet or liquid suspension of CLEC particles composed of a needed metabolic enzyme or protein. The CLEC agent would survive the harsh acidic pH and proteolytic environment of the stomach, and pass into the proximal small intestine. The CLEC particle would then carry out its therapeutic biochemistry within the gut lumen while remaining resistant to degradation by endogenous proteases. In this Phase I study, we propose to develop two types of CLECs: Oxalyl-CoA decarboxylase for oral lumenal therapy and Oxalate oxidase to be used in the extracorporeal device/dialysis equipment. The Oxalyl-CoA decarboxylase-CLEC will perform its action in the duodenum while remaining as crystalline material or by release of activity by dissolution of the CLEC particle. This target was chosen to address the problems of current therapies of hyperoxaluna caused by excessive absorption of oxalate due to the absence of Oxalobacter formigenes bacterium in the intestine or due to inflammatory bowel disease. In addition, Oxalate oxidase-CLEC may be used in dialysis equipment or extracorprealdevices to reduce the oxalate content of blood in patients with Primary Hyperoxaluria. If successful, these approaches will lead to the introduction of novel, efficient enzyme therapy for the prevention of Oxalate Kidney Stones. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE