New Method of Transcytosis Pathway and Ligand Discovery

描述(由申请人提供)：XenoPort将利用美国国立卫生研究院的资金开发一种新的噬菌体展示方法，用于识别口服治疗药物的有用的跨细胞途径，并用于识别治疗分子。目前口服大分子药物和其他肠道吸收较差的药物的方法不能提供足够的口服生物利用度。因此，必须确定运送大量化合物的新的肠道途径。不幸的是，目前的途径识别方法是不充分的。XenoPort将通过开发一种在噬菌体颗粒上展示合成分子的新方法来解决这个问题，以充分利用噬菌体展示分子库的精致敏感性和多功能性。这些文库将用于筛选受体的配体，通过肠道上皮引导最活跃的跨细胞途径，使一个商业就绪的技术平台的开发能够适应所有治疗领域的各种化合物。第一阶段研究为噬菌体展示化合物文库的构建、筛选和解码奠定了基础。第二阶段将开发和评估一个非常多样化的合成化合物的模型肽库，以促进发现活跃在内吞和跨细胞作用中的新配体。该技术将通过内部产品开发和战略合作伙伴关系实现商业化。

DESCRIPTION (provided by applicant): XenoPort will use NIH funding to develop a novel phage display method for identifying useful transcytotic pathways for oral administration of therapeutic drugs, and for identification of therapeutic molecules. Current methods for oral delivery of macromolecular and other drugs poorly absorbed by the intestine do not provide adequate oral bio-availability. Thus, new intestinal pathways to transport larger quantities of compound must be identified. Unfortunately, current methods of pathway identification are inadequate. XenoPort will address this problem by developing a new method for displaying synthetic molecules on phage particles to fully exploit the exquisite sensitivity and versatility of the phage for display of molecular libraries. These libraries will be used to screen for ligands to receptors directing the most active transcytosis pathways through the intestinal epithelium, enabling development of a commercial-ready technology platform adaptable to a wide variety of compounds in all therapeutic areas. Phase I studies established the fundamental method for constructing, screening and decoding libraries of synthetic compounds displayed on phage. Phase II will develop and evaluate a model peptide library of extraordinarily diverse synthetic compounds for enhanced discovery of novel ligands active in endocytosis and transcytosis. The technology will be commercialized via internal product development and strategic partnerships.