Monoclonal antibody to Factor B as a Therapeutic in Asthma

B 因子单克隆抗体可用于治疗哮喘

• 批准号: 7113123
• 负责人: Woodruff Emlen
• 金额: $ 28.76万
• 依托单位: TALIGEN THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113123
• 关键词: alternative complement pathway; asthma; biotechnology; complement inhibitors; disease /disorder model; drug design /synthesis /production; drug screening /evaluation; immunoglobulin G; immunologic substance development /preparation; immunopharmacology; immunotherapy; inhalation drug administration; laboratory mouse; monoclonal antibody; nonhuman therapy evaluation; ovalbumin; pharmacokinetics; respiratory disorder chemotherapy; respiratory pharmacology; therapy design /development

DESCRIPTION (provided by applicant): Asthma is a chronic, potentially debilitating disease caused by inflammation of the small airways, leading to the clinical symptoms of wheezing and shortness of breath. It is now estimated that asthma affects 20-25 million individuals in the United States and many more worldwide. The prevalence of the disease has nearly doubled in the past two decades and continues to increase inexorably. While the disease can be well-controlled in the majority of patients, currently available therapies do not adequately control symptoms in 5- 10% of patients with asthma, and these individuals in particular must be treated with high doses of corticosteroids in order to maintain adequate lung function. The worldwide market for various treatments of asthma was estimated and nearly $9 billion in 2003. Although the recent introduction of anti-lgE monoclonal antibody (mAb) therapy (Xolair) has been highly successful, both medically and commercially, asthma remains a debilitating and life-long affliction. Because of these issues, there remains a substantial unmet need for novel therapeutic approaches to treat asthma and the underlying inflammation which drives the disease. Recent studies have shown that mice deficient in the essential alternative complement pathway protein factor B are protected from the development of airway inflammation and hyperreactivity in models of asthma. Taligen collaborators Drs. Holers and Gelfand have also shown that use of a novel alternative pathway monoclonal antibody inhibitor (designated mAb 1379) directed to factor B results in amelioration of experimental asthma. Taligen Therapeutics, Inc. has negotiated an exclusive license with the University of Colorado Health Sciences Center and National Jewish Medical and Research Center to develop mAb 1379 for the treatment of asthma. This SBIR-at-NIAID proposal is directed at the development this antibody to factor B as a novel therapeutic approach for patients with asthma. This proposal will 1) define the optimum form of antibody to be administered in asthma models, 2) provide for humanization of this antibody and 3) confirm that the humanized form of the antibody is still equally as effective in the animal model of asthma as the original antibody. Following antibody humanization and confirmation of the therapeutic effectiveness of the humanized inhibitor, we will then be prepared for formal toxicology studies and submission of an IND

描述（由申请人提供）：哮喘是一种慢性、可能使人衰弱的疾病，由小气道炎症引起，导致喘息和呼吸短促的临床症状。据估计，美国有 20-2500 万人患有哮喘，全世界还有更多人患有哮喘。在过去二十年中，这种疾病的患病率几乎翻了一番，并且继续无情地增加。虽然大多数患者的疾病可以得到很好的控制，但目前可用的治疗方法并不能充分控制 5-10% 的哮喘患者的症状，特别是这些人必须接受高剂量的皮质类固醇治疗，以维持足够的哮喘治疗。肺功能。 2003 年，各种哮喘治疗方法的全球市场估计接近 90 亿美元。尽管最近推出的抗 lgE 单克隆抗体 (mAb) 疗法 (Xolair) 在医学上和商业上都取得了巨大成功，但哮喘仍然是一种令人衰弱和致命的疾病。 - 长期的痛苦。由于这些问题，对于治疗哮喘和导致该疾病的潜在炎症的新治疗方法仍然存在大量未满足的需求。 最近的研究表明，在哮喘模型中，缺乏必需的替代补体途径蛋白因子 B 的小鼠可以免受气道炎症和高反应性的发展。塔利根合作者博士。 Holers 和 Gelfand 还表明，使用针对 B 因子的新型替代途径单克隆抗体抑制剂（称为 mAb 1379）可改善实验性哮喘。 Taligen Therapeutics, Inc. 已与科罗拉多大学健康科学中心和国家犹太医学研究中心协商获得开发用于治疗哮喘的 mAb 1379 的独家许可。 NIAID 的 SBIR 提案旨在开发这种 B 因子抗体，作为哮喘患者的新型治疗方法。该提案将 1) 确定在哮喘模型中施用的最佳抗体形式，2) 提供该抗体的人源化，以及 3) 确认该抗体的人源化形式在哮喘动物模型中仍然与人源化抗体同样有效。原始抗体。在抗体人源化并确认人源化抑制剂的治疗效果后，我们将准备进行正式的毒理学研究并提交 IND