An Immunoadhesin Therapy for Inhalational Anthrax

描述(申请人提供)：Planet Biotech正在开发PBI-220，作为一种安全、有效和廉价的炭疽芽孢杆菌的治疗对策--炭疽杆菌是一种威胁美国平民人口的制剂。预计PBI-220对天然和工程炭疽毒素具有广谱活性。PBI-220是一种重组嵌合蛋白，是一种免疫粘附素，由人受体、针对致病靶点的诱饵和免疫球蛋白Fc组成，具有较长的循环半衰期和免疫效应细胞的相互作用。PBI-220由人的炭疽毒素受体CMG2胞外区和人IgG1的Fc组成。我们建议使用兔吸入性炭疽病模型来进一步证明转基因烟草来源的PBI-220的优越性能，然后通过关键的兔子研究通过直接比较来测试烟草来源的PBI-220和中国仓鼠卵巢(CHO)细胞来源的PBI-220的性能。我们将确定在孢子挑战后推迟治疗多长时间，同时仍能保护动物免于死亡。此外，我们还将直接比较植物制造的和CHO细胞制造的PBI-220的疗效。根据“动物法则”，这项研究将被认为是一项关键研究，并将被用来证明在一期临床试验中从一个或另一个来源测试PBI-220是合理的。

DESCRIPTION (provided by applicant): Planet Biotechnology is developing PBI-220 as a safe, effective and inexpensive therapeutic countermeasure to Bacillus anthracis - an agent threatening the U.S. civilian population. PBI-220 is expected to have broad spectrum activity against natural and engineered anthrax toxins. PBI-220, a recombinant chimeric protein, is an immunoadhesin comprised of a human receptor, a decoy against the pathogenic target, and an IgG-Fc, for a long circulating half-life and immune effector cell interaction. PBI-220 is comprised of the CMG2 extracellular domain, the human receptor for anthrax toxins, and the Fc of human IgGl. We propose to use the rabbit model of inhalation anthrax to further demonstrate the superior performance of PBI-220 derived from transgenic tobacco and then, to test, by direct comparison in a pivotal rabbit study, the performance of tobacco-derived and Chinese hamster ovary (CHO) cell-derived PBI-220. We will determine how long it is possible to delay treatment, following spore challenge, and still protect animals from death. In addition, we will directly compare the efficacy of the plant-made and CHO cell-made PBI-220s. This study will be considered a pivotal study, according to the "Animal Rule", and will be used to justify testing PBI-220, from one source or the other, in a Phase 1 clinical trial.