SBIR PHASE I: HIGH-CAPACITY MULTIMODAL ANION-EXCHANGE MEMBRANES FOR PURIFICATION OF BIOLOGICS

 描述（由申请人提供）：癌症、心血管和类风湿性疾病等慢性疾病的发病率不断上升，推动了对用于治疗这些疾病的生物制剂的需求。到2016年，美国前100种药物中有一半将是生物制剂，新产品的商业化将需要大幅扩大生产能力和提高生产灵活性，以满足未来的需求。此外，生物仿制药的出现将对生物制造商施加经济压力，要求他们创新新的纯化技术以降低生产成本。Purilogics（tm），LLC的长期目标是开发并将新的纯化技术推向市场，以提高生产能力和制造灵活性，同时降低生物药物的制造成本。在第一阶段，Purilogics提出开发一种新的吸附膜，用于生物制药下游加工。本研究的产品将是两种用于生物制品精制步骤的多模态阴离子交换膜。这些膜将区别于现有产品，因为它们具有行业最佳动态结合能力、高生产率、优异的耐盐性和对聚集体去除的高选择性等独特优势。该项目产生的一次性产品将简化当前工艺，无需进行除杂和聚合物去除步骤、色谱柱填充、再生和验证。一次性和模块化功能将使（合同）生物制造商能够调整净化能力，而无需大量资本支出。在第一阶段，Purilogics建议开发原型吸附膜组件，并通过与CharlestonPharma，LLC合作在内部和外部验证其性能。具体目标是（1）合成和表征具有独特配体的多峰阴离子交换膜吸附器，以及（2）制造和评估原型一次性吸附膜模块以进行验证。膜将通过用高密度的多峰聚合物链官能化大孔膜支撑物来合成。基准测试将评价关键性能指标：静态和动态结合能力以及在商业相关离子强度范围内杂质（宿主细胞蛋白质、DNA）的对数减少值。CharlestonPharma的外部验证将确定通过其专利抗体平台技术生产的癌症抗体产品的回收率、纯度和活性。将测定抗体聚集体、宿主细胞蛋白、内毒素和DNA杂质的去除。这项研究工作产生的创新产品将帮助生物制药制造商和合同生物制造商通过提高生产能力和制造灵活性来克服重大未满足的需求，同时相对于现有技术将纯化成本降低40%以上。从公共卫生的角度来看，影响是巨大的，因为提高生产能力和降低制造成本对于生产负担得起的治疗产品以改善公共卫生至关重要。

 DESCRIPTION (provided by applicant): Rising rates of chronic conditions such as cancer and cardiovascular and rheumatoid diseases are driving the demand for biologics used to treat them. Half of the top 100 drugs in the US will be biologics by 2016, and new product commercialization will require significant expansions in production capacity and improvements in manufacturing flexibility to meet future demands. In addition, the emergence of biosimilar will apply economic pressure on bio manufacturers to innovate new purification technologies to lower production costs. Purilogics(tm), LLC long-term objective is to develop and bring to market new purification technologies to increase production capacity and manufacturing flexibility and simultaneously lower the manufacturing cost of biologic drugs. In Phase I, Purilogics proposes to develop a new class of adsorptive membranes for use in biopharmaceutical downstream processing. The products of the effort will be two types' multimodal anion- exchange membranes for polishing step purification of biologics. These membranes will be differentiated from existing products because of their unique advantages of industry-best dynamic binding capacities, high productivity, excellent salt tolerance, and high selectivity for aggregates removal. The single-use products emanating from the project will simplify the current process by obviating the need for desalting and aggregate removal steps, column packing, regeneration and validation. The disposable and modular features will enable (contract) bio manufacturers to adjust purification capacity without significant capital expenditures. In Phase I, Purilogics proposes to develop prototype adsorptive membrane modules and validate their performance in-house and externally through collaboration with CharlestonPharma, LLC. The specific aims are to (1) synthesize and characterize multimodal anion-exchange membrane adsorbers with unique ligands and (2) fabricate and evaluate prototype single-use adsorptive membrane modules for validation. The membranes will be synthesized by functionalizing macroporous membrane supports with a high density of multimodal polymer chains. Benchmark testing will evaluate key performance metrics: static and dynamic binding capacities and log reduction values of impurities (host cell proteins, DNA) over a commercially relevant range of ionic strengths. External validation by CharlestonPharma will determine recovery, purity, and activity of cancer antibody products produced by their patented antibody platform technology. Removal of antibody aggregates, host cell proteins, endotoxins, and DNA impurities will be determined. The innovative products that result from this research effort will help biopharmaceutical manufacturers and contract bio manufacturers overcome significant unmet needs by increasing production capacity and manufacturing flexibility, while decreasing purification cost by >40% relative to existing technologies. The impact from a public health perspective is great, as increasing production capacity and decreasing manufacturing cost are essential to the production of affordable therapeutic products for improved public health.