High Expression Recombinant Factor VIII

高表达重组因子VIII

基本信息

批准号：
7481687
负责人：
Christopher Bradley Doering
金额：
$ 10万
依托单位：
EXPRESSION THERAPEUTICS
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-15 至 2009-04-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7481687
关键词：
Affect Anabolism Arts Biochemical Blood Clot Blood Coagulation Factor Blood Transfusion Blood coagulation Caring Cell Culture System Cells Cessation of life Child Clinical Cloning Conditioned Culture Media Data Development Disease Drops Elements Endothelin-1 Factor VIII Family suidae Genes Goals HIV Hamsters Hemophilia A Hemorrhage Hemostatic Agents Hepatitis C virus Human Hybrids Immune response In Vitro Individual Infection Infusion procedures Insecta Ion-Exchange Chromatography Procedure Joints Kidney Kinetics Knee Lead Letters Link Longevity M cell Mammalian Cell Medical Mission Modification Morbidity - disease rate Pathway interactions Patients Plasma Plasma Proteins Population Post-Translational Protein Processing Postoperative Period Preparation Price Process Production Proteins Protocols documentation Public Health Rate Recombinant Proteins Recombinants Risk Safety Secretory Cell Societies Standards of Weights and Measures System Technology Therapeutic Thrombin Time Transgenes Treatment Efficacy Tyrosine United States Week Yeasts arthropathies base concept cost domain mapping glycosylation human F8 protein immunogenicity improved intravenous administration novel recombinant antihemophilic factor VIII sulfation

项目摘要

DESCRIPTION (provided by applicant): The hemophilias (A and B) are rare bleeding disorders toward which much scientific and medical effort has been devoted. In 1840, blood transfusion was used for the first time to stop post-operative bleeding in a hemophilia patient and in 1968 the first commercial coagulation factor concentrate became available. The cloning of the fVIII gene in 1984 facilitated the development of recombinant fVIII protein products that became commercially available in 1992. This was viewed as a dramatic therapeutic improvement due to the perceived safety advantage recombinant products have over plasma-derived products, which proved responsible for the infection of thousands of patients with hemophilia with human immunodeficiency virus and/or hepatitis C virus during the 1980's. Since the development of recombinant fVIII, progress in the treatment of hemophilia A has slowed. The limitations of current treatment are 1) access to fVIII-replacement products, 2) the cost of fVIII- replacement products, 3) the development of humoral anti-fVIII immune responses that block treatment efficacy and 4) morbidity due to joint disease. State of the art treatment multiple infusions per week of fVIII product. However, many patients are treated only after the initiation of a bleeding episode and these patients typically develop joint arthropathy due to repeated bleeding into a target joint, e.g. knee. Unless the worldwide fVIII supply increases and prices drop significantly, hemophilia A will remain an important heath burden to human society. Therefore, the search for improved therapeutics is warranted. One strategy for improving hemophilia A care is to develop improved recombinant-protein products, e.g. manufactured more efficiently or have increased hemostatic efficacy. The mission of Expression Therapeutics is to develop products that will improve the treatment of individuals with hemophilia A. Our technology is based on the identification of sequence elements within fVIII that can be modified to increase its biosynthesis. The goal of the current study is to provide feasibility data supporting the concept that a high-expression fVIII-replacement product can be manufactured more efficiently than traditional human recombinant fVIII products. These data will support the development of a novel fVIII-replacement product that will improve the treatment of hemophilia A. PUBLIC HEALTH RELEVANCE: Hemophilia A is a bleeding disorder caused by the insufficiency of a blood clotting factor, designated factor VIII (fVIII). Current treatment for hemophilia relies on infusion of plasma-derived or recombinant fVIII products to restore circulating fVIII activity. Currently, treatment is offered to less than one-third of all patients with hemophilia A patients due to product cost. Unless the worldwide fVIII supply increases and prices drop significantly, hemophilia A will remain an important heath burden to human society and therefore the search for improved therapeutics is warranted.