Long Acting Beta Interferon for Treating Multiple Sclerosis - Phase II Continuing

描述（由申请人提供）：β干扰素是一种20kda的细胞因子，对许多细胞类型具有抗病毒、抗增殖和免疫调节作用。重组人β干扰素产品的全球年销售额为40亿美元，主要用于治疗多发性硬化症。干扰素在人体内的半衰期很短，因此需要频繁给药，而且可能无法使这种蛋白质对患者的治疗效果最优化。我们建议长效干扰素产品除了更方便的给药方案外，还可能为患者提供更好的治疗效果。在I期SBIR授权期间，我们确定了干扰素中可以用聚合物修饰的位点，而不会影响蛋白质的体外生物活性。在我们资助的第二阶段，我们开发了生产工艺，以生产足够数量的改良干扰素蛋白用于动物试验。这些研究表明，我们的聚合物修饰蛋白比领先的商业干扰素产品具有更长的半衰期，并且在动物疾病模型中明显比商业干扰素产品更有效。该II期持续更新提案的目标是在GLP（良好实验室规范）条件下生产该蛋白质，并在动物药理学和毒理学研究中测量该蛋白质的安全性和药代动力学特性，这是FDA在人体测试该化合物之前所要求的。我们的新型干扰素类似物的改进特性可能为多发性硬化症患者提供更有效和更方便的治疗方法。此外，该化合物有可能减少每位患者所需的干扰素量，降低毒性，降低免疫原性和中和抗体的发生率，提高患者的依从性和生活质量，并为患者和医疗保健提供者节省大量成本。这种长效干扰素类似物也可能被证明对癌症和病毒性疾病（如肝炎）的治疗有用。公共卫生相关性：重组干扰素用于治疗多发性硬化症患者，在美国估计有40万人受到影响。由于β干扰素在人体内的半衰期短，通常每周给患者皮下注射三次。我们创造了长效干扰素类似物，在动物疾病模型中明显比领先的商业干扰素更有效。该II期持续更新提案的目标是在GLP（良好实验室规范）条件下生产该蛋白质，并在动物药理学和毒理学研究中测量该蛋白质的安全性和药代动力学特性，这是FDA在人体测试该化合物之前所要求的。这种蛋白质可能为多发性硬化症患者提供更有效、更方便的治疗方法。

DESCRIPTION (provided by applicant): Beta interferon is a 20 kDa cytokine that exhibits antiviral, antiproliferative and immunomodulatory effects on many cell types. Recombinant human beta interferon products have annual worldwide sales of $4 billion, primarily from their use to treat Multiple Sclerosis. Beta interferon has a short half-life in humans, which necessitates frequent dosing and may not optimize therapeutic benefits of the protein for patients. We proposed that longer acting beta interferon products may provide patients with superior therapeutic benefits, in addition to a more convenient dosing regimen. During our Phase I SBIR grant we identified sites in beta interferon that can be modified with polymers without affecting the protein's in vitro bioactivity. During the Phase II portion of our grant, we developed manufacturing processes to produce sufficient quantities of the modified beta interferon proteins for testing in animals. These studies demonstrated that our polymer-modified protein has a longer half-life than a leading commercial beta interferon product and is significantly more effective than the commercial beta interferon product in an animal disease model. The goals of this Phase II continuing renewal proposal are to manufacture the protein under GLP (Good Laboratory Practices) conditions and measure the safety profile and pharmacokinetic properties of the protein in animal pharmacology and toxicology studies, which are required by the FDA prior to testing the compound in humans. The improved characteristics of our novel beta interferon analog may provide Multiple Sclerosis patients with a more effective and more convenient therapy for treatment of their disease. In addition, this compound has the potential to reduce the amount of beta interferon required per patient, reduce toxicity, reduce immunogenicity and incidence of neutralizing antibodies, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. This long-acting beta interferon analog also may prove useful for the treatment of cancer and viral diseases such as hepatitis. PUBLIC HEALTH RELEVANCE: Recombinant beta interferon is used to treat patients with Multiple Sclerosis, which affects an estimated 400,000 people in the United States. Beta interferon typically is administered to patients by thrice weekly subcutaneous injection due to its short half-life in people. We created longer acting beta interferon analogs that are significantly more efficacious than a leading commercial beta interferon in animal disease models. The goals of this Phase II continuing renewal proposal are to manufacture the protein under GLP (Good Laboratory Practices) conditions and measure the safety profile and pharmacokinetic properties of the protein in animal pharmacology and toxicology studies, which are required by the FDA prior to testing the compound in humans. This protein may provide Multiple Sclerosis patients with a more effective and more convenient therapy for the treatment their disease.