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

长效 β 干扰素治疗多发性硬化症 - II 期继续

基本信息

批准号：
7684226
负责人：
George Norbert Cox
金额：
$ 79.08万
依托单位：
BOLDER BIOTECHNOLOGY, INC.
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7684226
关键词：
Affect Amino Acids Animal Disease Models Animals Anions Antiviral Agents Biological Biological Assay Biotechnology Brain Injuries Capital Characteristics Chemicals Clinical Clinical Investigator Clinical Trials Clinical Trials Design Clinical trial protocol document Column Chromatography Core Protein Cost Savings Cysteine Data Development Disease Disease Progression Dose Drug Formulations Drug Kinetics Drug usage Effectiveness Employee Strikes Endotoxins Ensure Enzyme-Linked Immunosorbent Assay Escherichia coli Escherichia coli Proteins Evaluation Exhibits Experimental Autoimmune Encephalomyelitis FDA approved Fermentation Funding Goals Government Grant Growth Half-Life Health Personnel Hepatitis High Pressure Liquid Chromatography Human In Vitro Incidence Injection of therapeutic agent Interferon-beta Laboratories Lead Liquid substance Measures Modeling Modification Multiple Sclerosis Mus Patients Persons Pharmacology and Toxicology Phase Phenylalanine Polyethylene Glycols Polymers Positioning Attribute Post-Translational Protein Processing Procedures Process Property Protein Region Proteins Quality of life Rattus Recombinant Interferon Beta Recombinant interferon beta-1b Recombinants Relapse Rodent Safety Sales Serine Serum Site Site-Directed Mutagenesis Small Business Innovation Research Grant Societies Solutions Staging Subcutaneous Injections Sulfhydryl Compounds Testing Therapeutic Toxic effect Toxicology Treatment Protocols United States Validation Viral Virus Diseases Writing analog analytical method base cancer therapy cell growth cell type compliance behavior cytokine design disulfide bond effective therapy flasks good laboratory practice immunogenicity improved in vivo manufacturing process meetings neoplastic cell neutralizing antibody nonhuman primate novel pre-clinical preclinical study public health relevance receptor binding subcutaneous technical report tumor tumor growth

项目摘要

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.

描述（由申请方提供）：β干扰素是一种20 kDa的细胞因子，对多种细胞类型具有抗病毒、抗增殖和免疫调节作用。重组人β干扰素产品在全球的年销售额为40亿美元，主要来自其用于治疗多发性硬化症。β干扰素在人体中的半衰期较短，需要频繁给药，并且可能无法优化蛋白质对患者的治疗益处。我们认为长效β干扰素产品除了给药方案更方便外，还可为患者提供上级治疗益处。在我们的第一阶段SBIR资助期间，我们确定了β干扰素中可以用聚合物修饰而不影响蛋白质的体外生物活性的位点。在第二阶段，我们开发了生产工艺，以生产足够数量的修饰β干扰素蛋白质用于动物试验。这些研究表明，我们的聚合物修饰的蛋白质具有比领先的商业β干扰素产品更长的半衰期，并且在动物疾病模型中比商业β干扰素产品显著更有效。该II期持续更新提案的目标是在GLP（良好实验室规范）条件下生产蛋白质，并在动物药理学和毒理学研究中测量蛋白质的安全性和药代动力学特性，这是FDA在人体测试化合物之前所要求的。我们的新型β干扰素类似物的改进特性可以为多发性硬化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β干扰素的量，降低毒性，降低免疫原性和中和抗体的发生率，改善患者依从性和生活质量，并为患者和医疗保健提供者节省大量成本。这种长效β干扰素类似物也可能被证明对治疗癌症和病毒性疾病如肝炎有用。公共卫生相关性：重组β干扰素用于治疗多发性硬化症患者，在美国估计有40万人患有多发性硬化症。由于β干扰素在人体内的半衰期短，通常通过每周三次皮下注射给予患者。我们创造了更长效的β干扰素类似物，在动物疾病模型中比领先的商业β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）条件下生产蛋白质，并在动物药理学和毒理学研究中测量蛋白质的安全性和药代动力学特性，这是FDA在人体测试化合物之前所要求的。这种蛋白质可能为多发性硬化患者提供更有效和更方便的治疗方法。