Monoclonal Antibody to Factor B as Therapeutic in Asthma

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