Novel pharmacogenomic approach for identifying T cell epitopes in replacement FVI

DESCRIPTION (provided by applicant): About 30% of congenital Hemophilia A (HA) patients develop alloantibodies that neutralize the activity of replacement Factor (F) VIII proteins. Among African American HA patients, the frequency of inhibitor formation ismuch higher; about 50%. Inhibitor patients are typically treated with bypassing agents. Bypassing agents are more expensive and less effective than FVIII in fully controlling bleeding. Chronic bleeding into joints causes inhibitor patients to require more orthopedic surgeries and to experience reduced mobility, in comparison to HA patients who can be managed with replacement FVIII. Despite the introduction of some 40 FVIII products, the rate of inhibitor formation has remained constant since the 1970s. Undergoing a lengthy, arduous and very expensive therapy, known as immune tolerance induction (ITI), is the only means available to eradicate inhibitors in HA patients. The amount of FVIII required for ITI and the intensity of the treatment result in co